ProFi Achievements
Publications
2021 |
Mori, Daiki; Grégoire, Claude; Voisinne, Guillaume; Celis-Gutierrez, Javier; Aussel, Rudy; Girard, Laura; è, Myl; è, Marl; Argenty, Jérémy; Burlet-Schiltz, Odile; Fiore, Frédéric; de Peredo, Anne; Malissen, Marie; Roncagalli, Romain; Malissen, Bernard The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation. Article de journal The Journal of experimental medicine, 218 (2), 2021. @article{Mori2021, title = {The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation.}, author = {Daiki Mori and Claude Grégoire and Guillaume Voisinne and Javier Celis-Gutierrez and Rudy Aussel and Laura Girard and Myl{è}ne Camus and Marl{è}ne Marcellin and Jérémy Argenty and Odile Burlet-Schiltz and Frédéric Fiore and Anne de Peredo and Marie Malissen and Romain Roncagalli and Bernard Malissen}, doi = {10.1084/jem.20201011}, year = {2021}, date = {2021-01-01}, journal = {The Journal of experimental medicine}, volume = {218}, number = {2}, abstract = {To determine the respective contribution of the LAT transmembrane adaptor and CD5 and CD6 transmembrane receptors to early TCR signal propagation, diversification, and termination, we describe a CRISPR/Cas9-based platform that uses primary mouse T cells and permits establishment of the composition of their LAT, CD5, and CD6 signalosomes in only 4 mo using quantitative mass spectrometry. We confirmed that positive and negative functions can be solely assigned to the LAT and CD5 signalosomes, respectively. In contrast, the TCR-inducible CD6 signalosome comprised both positive (SLP-76, ZAP70, VAV1) and negative (UBASH3A/STS-2) regulators of T cell activation. Moreover, CD6 associated independently of TCR engagement to proteins that support its implication in inflammatory pathologies necessitating T cell transendothelial migration. The multifaceted role of CD6 unveiled here accounts for past difficulties in classifying it as a coinhibitor or costimulator. Congruent with our identification of UBASH3A within the CD6 signalosome and the view that CD6 constitutes a promising target for autoimmune disease treatment, single-nucleotide polymorphisms associated with human autoimmune diseases have been found in the Cd6 and Ubash3a genes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } To determine the respective contribution of the LAT transmembrane adaptor and CD5 and CD6 transmembrane receptors to early TCR signal propagation, diversification, and termination, we describe a CRISPR/Cas9-based platform that uses primary mouse T cells and permits establishment of the composition of their LAT, CD5, and CD6 signalosomes in only 4 mo using quantitative mass spectrometry. We confirmed that positive and negative functions can be solely assigned to the LAT and CD5 signalosomes, respectively. In contrast, the TCR-inducible CD6 signalosome comprised both positive (SLP-76, ZAP70, VAV1) and negative (UBASH3A/STS-2) regulators of T cell activation. Moreover, CD6 associated independently of TCR engagement to proteins that support its implication in inflammatory pathologies necessitating T cell transendothelial migration. The multifaceted role of CD6 unveiled here accounts for past difficulties in classifying it as a coinhibitor or costimulator. Congruent with our identification of UBASH3A within the CD6 signalosome and the view that CD6 constitutes a promising target for autoimmune disease treatment, single-nucleotide polymorphisms associated with human autoimmune diseases have been found in the Cd6 and Ubash3a genes. |
Froment, Carine; Zanolli, Clément; Hourset, Mathilde; Mouton-Barbosa, Emmanuelle; Moreira, Andreia; Burlet-Schiltz, Odile; Mollereau, Catherine Protein sequence comparison of human and non-human primate tooth proteomes. Article de journal Journal of proteomics, 231 , p. 104045, 2021. @article{Froment2021, title = {Protein sequence comparison of human and non-human primate tooth proteomes.}, author = {Carine Froment and Clément Zanolli and Mathilde Hourset and Emmanuelle Mouton-Barbosa and Andreia Moreira and Odile Burlet-Schiltz and Catherine Mollereau}, doi = {10.1016/j.jprot.2020.104045}, year = {2021}, date = {2021-01-01}, journal = {Journal of proteomics}, volume = {231}, pages = {104045}, address = {Netherlands}, abstract = {In the context of human evolution, the study of proteins may overcome the limitation of the high degradation of ancient DNA over time to provide biomolecular information useful for the phylogenetic reconstruction of hominid taxa. In this study, we used a shotgun proteomics approach to compare the tooth proteomes of extant human and non-human primates (gorilla, chimpanzee, orangutan and baboon) in order to search for a panel of peptides able to discriminate between taxa and further help reconstructing the evolutionary relationships of fossil primates. Among the 25 proteins shared by the five genera datasets, we found a combination of peptides with sequence variations allowing to differentiate the hominid taxa in the proteins AHSG, AMBN, APOA1, BGN, C9, COL11A2, COL22A1, COL3A1, DSPP, F2, LUM, OMD, PCOLCE and SERPINA1. The phylogenetic tree confirms the placement of the samples in the appropriate genus branches. Altogether, the results provide experimental evidence that a shotgun proteomics approach on dental tissue has the potential to detect taxonomic variation, which is promising for future investigations of uncharacterized and/or fossil hominid/hominin specimens. SIGNIFICANCE: A shotgun proteomics approach on human and non-human primate teeth allowed to identify peptides with taxonomic interest, highlighting the potential for future studies on hominid fossils.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In the context of human evolution, the study of proteins may overcome the limitation of the high degradation of ancient DNA over time to provide biomolecular information useful for the phylogenetic reconstruction of hominid taxa. In this study, we used a shotgun proteomics approach to compare the tooth proteomes of extant human and non-human primates (gorilla, chimpanzee, orangutan and baboon) in order to search for a panel of peptides able to discriminate between taxa and further help reconstructing the evolutionary relationships of fossil primates. Among the 25 proteins shared by the five genera datasets, we found a combination of peptides with sequence variations allowing to differentiate the hominid taxa in the proteins AHSG, AMBN, APOA1, BGN, C9, COL11A2, COL22A1, COL3A1, DSPP, F2, LUM, OMD, PCOLCE and SERPINA1. The phylogenetic tree confirms the placement of the samples in the appropriate genus branches. Altogether, the results provide experimental evidence that a shotgun proteomics approach on dental tissue has the potential to detect taxonomic variation, which is promising for future investigations of uncharacterized and/or fossil hominid/hominin specimens. SIGNIFICANCE: A shotgun proteomics approach on human and non-human primate teeth allowed to identify peptides with taxonomic interest, highlighting the potential for future studies on hominid fossils. |
è, Hél; Blanckaert, Vincent; Veidl, Brigitte; Burlet-Schiltz, Odile; Pichereaux, Carole; Gargaros, Audrey; Marchand, Justine; î, Beno Application of pulsed electric fields for the biocompatible extraction of proteins from the microalga Haematococcus pluvialis. Article de journal Bioelectrochemistry (Amsterdam, Netherlands), 137 , p. 107588, 2021. @article{Gateau2021, title = {Application of pulsed electric fields for the biocompatible extraction of proteins from the microalga Haematococcus pluvialis.}, author = {Hél{è}ne Gateau and Vincent Blanckaert and Brigitte Veidl and Odile Burlet-Schiltz and Carole Pichereaux and Audrey Gargaros and Justine Marchand and Beno{î}t Schoefs}, doi = {10.1016/j.bioelechem.2020.107588}, year = {2021}, date = {2021-01-01}, journal = {Bioelectrochemistry (Amsterdam, Netherlands)}, volume = {137}, pages = {107588}, address = {Netherlands}, abstract = {This study aims to employ a pulsed electric field (PEF) treatment for the biocompatible (non-destructive) extraction of proteins from living cells of the green microalga Haematococcus pluvialis. Using a field strength of 1 kV cm(-1), we achieved the extraction of 10.2 µg protein per mL of culture, which corresponded to 46% of the total amount of proteins that could be extracted by complete destructive extraction (i.e. the grinding of biomass with glass beads). We found that the extraction yield was not improved by stronger field strengths and was not dependent on the pulse frequency. A biocompatibility index (BI) was defined as the relative abundance of cells that remained alive after the PEF treatment. This index relied on measurements of several physiological parameters after a PEF treatment. It was found that at 1 kV cm(-1) that cultures recovered after 72 h. Therefore, these PEF conditions constituted a good compromise between protein extraction efficiency and culture survival. To characterize the PEF treatment further at a molecular level, mass spectrometry-based proteomics analyses of PEF-prepared extracts was used. This led to the identification of 52 electro-extracted proteins. Of these, only 16 proteins were identified when proteins were extracted with PEF at 0.5 cm(-1). They belong to core metabolism, stress response and cell movement. Unassigned proteins were also extracted. Their physiological implications and possible utilization in food as alimentary complements are discussed.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This study aims to employ a pulsed electric field (PEF) treatment for the biocompatible (non-destructive) extraction of proteins from living cells of the green microalga Haematococcus pluvialis. Using a field strength of 1 kV cm(-1), we achieved the extraction of 10.2 µg protein per mL of culture, which corresponded to 46% of the total amount of proteins that could be extracted by complete destructive extraction (i.e. the grinding of biomass with glass beads). We found that the extraction yield was not improved by stronger field strengths and was not dependent on the pulse frequency. A biocompatibility index (BI) was defined as the relative abundance of cells that remained alive after the PEF treatment. This index relied on measurements of several physiological parameters after a PEF treatment. It was found that at 1 kV cm(-1) that cultures recovered after 72 h. Therefore, these PEF conditions constituted a good compromise between protein extraction efficiency and culture survival. To characterize the PEF treatment further at a molecular level, mass spectrometry-based proteomics analyses of PEF-prepared extracts was used. This led to the identification of 52 electro-extracted proteins. Of these, only 16 proteins were identified when proteins were extracted with PEF at 0.5 cm(-1). They belong to core metabolism, stress response and cell movement. Unassigned proteins were also extracted. Their physiological implications and possible utilization in food as alimentary complements are discussed. |
2020 |
Zhai, Yunhao; Celis-Gutierrez, Javier; Voisinne, Guillaume; Mori, Daiki; Girard, Laura; Burlet-Schiltz, Odile; de Peredo, Anne Gonzalez; Roncagalli, Romain; Malissen, Bernard Opposing regulatory functions of the TIM3 (HAVCR2) signalosome in primary effector T cells as revealed by quantitative interactomics. Article de journal Cellular & molecular immunology, 2020. @article{Zhai2020, title = {Opposing regulatory functions of the TIM3 (HAVCR2) signalosome in primary effector T cells as revealed by quantitative interactomics.}, author = {Yunhao Zhai and Javier Celis-Gutierrez and Guillaume Voisinne and Daiki Mori and Laura Girard and Odile Burlet-Schiltz and Anne Gonzalez de Peredo and Romain Roncagalli and Bernard Malissen}, doi = {10.1038/s41423-020-00575-7}, year = {2020}, date = {2020-11-01}, journal = {Cellular & molecular immunology}, address = {China}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Eren, Elif; è, Rémi Plan; Bagayoko, Salimata; Bordignon, Pierre-Jean; Chaoui, Karima; Hessel, Audrey; Santoni, Karin; Pinilla, Miriam; Lagrange, Brice; Burlet-Schiltz, Odile; Howard, Jonathan C; Henry, Thomas; Yamamoto, Masahiro; Meunier, Etienne Irgm2 and Gate-16 cooperatively dampen Gram-negative bacteria-induced caspase-11 response. Article de journal EMBO reports, 21 (11), p. e50829, 2020. @article{Eren2020, title = {Irgm2 and Gate-16 cooperatively dampen Gram-negative bacteria-induced caspase-11 response.}, author = {Elif Eren and Rémi Plan{è}s and Salimata Bagayoko and Pierre-Jean Bordignon and Karima Chaoui and Audrey Hessel and Karin Santoni and Miriam Pinilla and Brice Lagrange and Odile Burlet-Schiltz and Jonathan C Howard and Thomas Henry and Masahiro Yamamoto and Etienne Meunier}, doi = {10.15252/embr.202050829}, year = {2020}, date = {2020-11-01}, journal = {EMBO reports}, volume = {21}, number = {11}, pages = {e50829}, abstract = {Inflammatory caspase-11 (rodent) and caspases-4/5 (humans) detect the Gram-negative bacterial component LPS within the host cell cytosol, promoting activation of the non-canonical inflammasome. Although non-canonical inflammasome-induced pyroptosis and IL-1-related cytokine release are crucial to mount an efficient immune response against various bacteria, their unrestrained activation drives sepsis. This suggests that cellular components tightly control the threshold level of the non-canonical inflammasome in order to ensure efficient but non-deleterious inflammatory responses. Here, we show that the IFN-inducible protein Irgm2 and the ATG8 family member Gate-16 cooperatively counteract Gram-negative bacteria-induced non-canonical inflammasome activation, both in cultured macrophages and in vivo. Specifically, the Irgm2/Gate-16 axis dampens caspase-11 targeting to intracellular bacteria, which lowers caspase-11-mediated pyroptosis and cytokine release. Deficiency in Irgm2 or Gate16 induces both guanylate binding protein (GBP)-dependent and GBP-independent routes for caspase-11 targeting to intracellular bacteria. Our findings identify molecular effectors that fine-tune bacteria-activated non-canonical inflammasome responses and shed light on the understanding of the immune pathways they control.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Inflammatory caspase-11 (rodent) and caspases-4/5 (humans) detect the Gram-negative bacterial component LPS within the host cell cytosol, promoting activation of the non-canonical inflammasome. Although non-canonical inflammasome-induced pyroptosis and IL-1-related cytokine release are crucial to mount an efficient immune response against various bacteria, their unrestrained activation drives sepsis. This suggests that cellular components tightly control the threshold level of the non-canonical inflammasome in order to ensure efficient but non-deleterious inflammatory responses. Here, we show that the IFN-inducible protein Irgm2 and the ATG8 family member Gate-16 cooperatively counteract Gram-negative bacteria-induced non-canonical inflammasome activation, both in cultured macrophages and in vivo. Specifically, the Irgm2/Gate-16 axis dampens caspase-11 targeting to intracellular bacteria, which lowers caspase-11-mediated pyroptosis and cytokine release. Deficiency in Irgm2 or Gate16 induces both guanylate binding protein (GBP)-dependent and GBP-independent routes for caspase-11 targeting to intracellular bacteria. Our findings identify molecular effectors that fine-tune bacteria-activated non-canonical inflammasome responses and shed light on the understanding of the immune pathways they control. |
Klein, Julie; Caubet, Cécile; è, Myl; Makridakis, Manousos; Denis, Colette; Gilet, Marion; è, Guyl; Rascalou, Simon; Neau, Eric; Garrigues, Luc; du Boullay, Olivier; Mischak, Harald; Monsarrat, Bernard; Burlet-Schiltz, Odile; Vlahou, Antonia; Saulnier-Blache, Jean Sébastien; Bascands, Jean-Loup; Schanstra, Joost P Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease. Article de journal Scientific reports, 10 (1), p. 14898, 2020. @article{Klein2020, title = {Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease.}, author = {Julie Klein and Cécile Caubet and Myl{è}ne Camus and Manousos Makridakis and Colette Denis and Marion Gilet and Guyl{è}ne Feuillet and Simon Rascalou and Eric Neau and Luc Garrigues and Olivier du Boullay and Harald Mischak and Bernard Monsarrat and Odile Burlet-Schiltz and Antonia Vlahou and Jean Sébastien Saulnier-Blache and Jean-Loup Bascands and Joost P Schanstra}, doi = {10.1038/s41598-020-71950-7}, year = {2020}, date = {2020-09-01}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {14898}, abstract = {While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). The raw data are publicly available via ProteomeXchange with identifier PXD018728. We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs's signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthenolide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs's signature. Oral treatment of 2 months old Ins2Akita mice with dimethylaminoparthenolide (DMAPT, a water-soluble analogue of parthenolide) for two months at 10 mg/kg/d by gavage significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach, we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD.}, keywords = {}, pubstate = {published}, tppubtype = {article} } While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). The raw data are publicly available via ProteomeXchange with identifier PXD018728. We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs's signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthenolide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs's signature. Oral treatment of 2 months old Ins2Akita mice with dimethylaminoparthenolide (DMAPT, a water-soluble analogue of parthenolide) for two months at 10 mg/kg/d by gavage significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach, we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD. |
Bouyssié, D; Hesse, A M; Mouton-Barbosa, E; Rompais, M; Macron, C; Carapito, C; de Peredo, A G; Couté, Y; Dupierris, V; Burel, A; Menetrey, J P; Kalaitzakis, A; Poisat, J; Romdhani, A; Burlet-Schiltz, O; Cianférani, S; Garin, J; Bruley, C Proline: an efficient and user-friendly software suite for large-scale proteomics Article de journal Bioinformatics, 36 (10), p. 3148-3155, 2020. @article{pmid32096818, title = {Proline: an efficient and user-friendly software suite for large-scale proteomics}, author = {D Bouyssié and A M Hesse and E Mouton-Barbosa and M Rompais and C Macron and C Carapito and A G de Peredo and Y Couté and V Dupierris and A Burel and J P Menetrey and A Kalaitzakis and J Poisat and A Romdhani and O Burlet-Schiltz and S Cianférani and J Garin and C Bruley}, doi = {10.1093/bioinformatics/btaa118}, year = {2020}, date = {2020-05-01}, journal = {Bioinformatics}, volume = {36}, number = {10}, pages = {3148-3155}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Pirro, M; Rombouts, Y; Stella, A; Neyrolles, O; Burlet-Schiltz, O; van Vliet, S J; de Ru, A H; Mohammed, Y; Wuhrer, M; van Veelen, P A; Hensbergen, P J Characterization of Macrophage Galactose-type Lectin (MGL) ligands in colorectal cancer cell lines Article de journal Biochim Biophys Acta Gen Subj, 1864 (4), p. 129513, 2020. @article{pmid31911241, title = {Characterization of Macrophage Galactose-type Lectin (MGL) ligands in colorectal cancer cell lines}, author = {M Pirro and Y Rombouts and A Stella and O Neyrolles and O Burlet-Schiltz and S J van Vliet and A H de Ru and Y Mohammed and M Wuhrer and P A van Veelen and P J Hensbergen}, doi = {10.1016/j.bbagen.2020.129513}, year = {2020}, date = {2020-04-03}, journal = {Biochim Biophys Acta Gen Subj}, volume = {1864}, number = {4}, pages = {129513}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Locard-Paulet, Marie; Bouyssié, David; Froment, Carine; Burlet-Schiltz, Odile; Jensen, Lars J Comparing 22 Popular Phosphoproteomics Pipelines for Peptide Identification and Site Localization. Article de journal Journal of proteome research, 19 (3), p. 1338–1345, 2020. @article{Locard-Paulet2020a, title = {Comparing 22 Popular Phosphoproteomics Pipelines for Peptide Identification and Site Localization.}, author = {Marie Locard-Paulet and David Bouyssié and Carine Froment and Odile Burlet-Schiltz and Lars J Jensen}, doi = {10.1021/acs.jproteome.9b00679}, year = {2020}, date = {2020-03-01}, journal = {Journal of proteome research}, volume = {19}, number = {3}, pages = {1338--1345}, address = {United States}, abstract = {Phosphorylation-driven cell signaling governs most biological functions and is widely studied using mass-spectrometry-based phosphoproteomics. Identifying the peptides and localizing the phosphorylation sites within them from the raw data is challenging and can be performed by several algorithms that return scores that are not directly comparable. This increases the heterogeneity among published phosphoproteomics data sets and prevents their direct integration. Here we compare 22 pipelines implemented in the main software tools used for bottom-up phosphoproteomics analysis (MaxQuant, Proteome Discoverer, PeptideShaker). We test six search engines (Andromeda, Comet, Mascot, MS Amanda, SequestHT, and X!Tandem) in combination with several localization scoring algorithms (delta score, D-score, PTM-score, phosphoRS, and Ascore). We show that these follow very different score distributions, which can lead to different false localization rates for the same threshold. We provide a strategy to discriminate correctly from incorrectly localized phosphorylation sites in a consistent manner across the tested pipelines. The results presented here can help users choose the most appropriate pipeline and cutoffs for their phosphoproteomics analysis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Phosphorylation-driven cell signaling governs most biological functions and is widely studied using mass-spectrometry-based phosphoproteomics. Identifying the peptides and localizing the phosphorylation sites within them from the raw data is challenging and can be performed by several algorithms that return scores that are not directly comparable. This increases the heterogeneity among published phosphoproteomics data sets and prevents their direct integration. Here we compare 22 pipelines implemented in the main software tools used for bottom-up phosphoproteomics analysis (MaxQuant, Proteome Discoverer, PeptideShaker). We test six search engines (Andromeda, Comet, Mascot, MS Amanda, SequestHT, and X!Tandem) in combination with several localization scoring algorithms (delta score, D-score, PTM-score, phosphoRS, and Ascore). We show that these follow very different score distributions, which can lead to different false localization rates for the same threshold. We provide a strategy to discriminate correctly from incorrectly localized phosphorylation sites in a consistent manner across the tested pipelines. The results presented here can help users choose the most appropriate pipeline and cutoffs for their phosphoproteomics analysis. |
Ibrahim, M; Ayoub, D; Wasselin, T; Dorsselaer, Van A; Maho, Le Y; Raclot, T; Bertile, F Alterations in rat adipose tissue transcriptome and proteome in response to prolonged fasting Article de journal Biological Chemistry, 401 (3), p. 389-405, 2020. @article{643, title = {Alterations in rat adipose tissue transcriptome and proteome in response to prolonged fasting}, author = {M Ibrahim and D Ayoub and T Wasselin and A Van Dorsselaer and Y Le Maho and T Raclot and F Bertile}, doi = {10.1515/hsz-2019-0184}, year = {2020}, date = {2020-02-25}, journal = {Biological Chemistry}, volume = {401}, number = {3}, pages = {389-405}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Bonnet, M; Soulat, J; Bons, J; Leger, S; Koning, De L; Carapito, C; Picard, B Quantification of biomarkers for beef meat qualities using a combination of Parallel Reaction Monitoring- and antibody-based proteomics Article de journal Food Chem, 317 , p. 126376., 2020. @article{641, title = {Quantification of biomarkers for beef meat qualities using a combination of Parallel Reaction Monitoring- and antibody-based proteomics}, author = {M Bonnet and J Soulat and J Bons and S Leger and L De Koning and C Carapito and B Picard}, doi = {10.1016/j.foodchem.2020.126376}, year = {2020}, date = {2020-02-10}, journal = {Food Chem}, volume = {317}, pages = {126376.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Locard-Paulet, M; Bouyssié, D; Froment, C; Burlet-Schiltz, O; Jensen, L J Comparing 22 Popular Phosphoproteomics Pipelines for Peptide Identification and Site Localization Article de journal J. Proteome Res., 19 (3), p. 1338–1345, 2020. @article{pmid31975593, title = {Comparing 22 Popular Phosphoproteomics Pipelines for Peptide Identification and Site Localization}, author = {M Locard-Paulet and D Bouyssié and C Froment and O Burlet-Schiltz and L J Jensen}, doi = {10.1021/acs.jproteome.9b00679}, year = {2020}, date = {2020-02-04}, journal = {J. Proteome Res.}, volume = {19}, number = {3}, pages = {1338--1345}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Imbert, C; Montfort, A; Fraisse, M; Marcheteau, E; Gilhodes, J; Martin, E; Bertrand, F; Marcellin, M; Burlet-Schiltz, O; Peredo, A G; Garcia, V; Carpentier, S; Tartare-Deckert, S; Brousset, P; Rochaix, P; Puisset, F; Filleron, T; Meyer, N; Lamant, L; Levade, T; Ségui, B; Andrieu-Abadie, N; Colacios, C Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1 Article de journal Nat Commun, 11 (1), p. 437, 2020. @article{pmid31974367, title = {Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1}, author = {C Imbert and A Montfort and M Fraisse and E Marcheteau and J Gilhodes and E Martin and F Bertrand and M Marcellin and O Burlet-Schiltz and A G Peredo and V Garcia and S Carpentier and S Tartare-Deckert and P Brousset and P Rochaix and F Puisset and T Filleron and N Meyer and L Lamant and T Levade and B Ségui and N Andrieu-Abadie and C Colacios}, doi = { 10.1038/s41467-019-14218-7}, year = {2020}, date = {2020-01-23}, journal = {Nat Commun}, volume = {11}, number = {1}, pages = {437}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Froment, C; Hourset, M; S?enz-Oyh?r?guy, N; Mouton-Barbosa, E; Willmann, C; Zanolli, C; Esclassan, R; Donat, R; Th?ves, C; Burlet-Schiltz, O; Mollereau, C Analysis of 5000 year-old human teeth using optimized large-scale and targeted proteomics approaches for detection of sex-specific peptides Article de journal J Proteomics, 211 , p. 103548, 2020. @article{pmid31626997, title = {Analysis of 5000 year-old human teeth using optimized large-scale and targeted proteomics approaches for detection of sex-specific peptides}, author = {C Froment and M Hourset and N S?enz-Oyh?r?guy and E Mouton-Barbosa and C Willmann and C Zanolli and R Esclassan and R Donat and C Th?ves and O Burlet-Schiltz and C Mollereau}, doi = {10.1016/j.jprot.2019.103548}, year = {2020}, date = {2020-01-16}, journal = {J Proteomics}, volume = {211}, pages = {103548}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Clement, E; Lazar, I; Attané, C; Carrié, L; Dauvillier, S; Ducoux-Petit, M; Estève, D; Menneteau, T; Moutahir, M; Gonidec, Le S; Dalle, S; Valet, P; Burlet-Schiltz, O; Muller, C; Nieto, L Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells Article de journal EMBO J., 39 (3), p. e102525, 2020. @article{pmid31919869, title = {Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells}, author = {E Clement and I Lazar and C Attané and L Carrié and S Dauvillier and M Ducoux-Petit and D Estève and T Menneteau and M Moutahir and S Le Gonidec and S Dalle and P Valet and O Burlet-Schiltz and C Muller and L Nieto}, doi = {10.15252/embj.2019102525}, year = {2020}, date = {2020-01-10}, journal = {EMBO J.}, volume = {39}, number = {3}, pages = {e102525}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Santin, Yohan; Fazal, Loubina; Sainte-Marie, Yannis; Sicard, Pierre; Maggiorani, Damien; Tortosa, Florence; Yücel, Yasemin Yücel; Teyssedre, Lise; Rouquette, Jacques; Marcellin, Marlene; Vindis, Cécile; Shih, Jean C; Lairez, Olivier; Burlet-Schiltz, Odile; Parini, Angelo; Lezoualc'h, Frank; Mialet-Perez, Jeanne Mitochondrial 4-HNE derived from MAO-A promotes mitoCa(2+) overload in chronic postischemic cardiac remodeling. Article de journal Cell death and differentiation, 27 (6), p. 1907–1923, 2020. @article{Santin2020, title = {Mitochondrial 4-HNE derived from MAO-A promotes mitoCa(2+) overload in chronic postischemic cardiac remodeling.}, author = {Yohan Santin and Loubina Fazal and Yannis Sainte-Marie and Pierre Sicard and Damien Maggiorani and Florence Tortosa and Yasemin Yücel Yücel and Lise Teyssedre and Jacques Rouquette and Marlene Marcellin and Cécile Vindis and Jean C Shih and Olivier Lairez and Odile Burlet-Schiltz and Angelo Parini and Frank Lezoualc'h and Jeanne Mialet-Perez}, doi = {10.1038/s41418-019-0470-y}, year = {2020}, date = {2020-01-01}, journal = {Cell death and differentiation}, volume = {27}, number = {6}, pages = {1907--1923}, abstract = {Chronic remodeling postmyocardial infarction consists in various maladaptive changes including interstitial fibrosis, cardiomyocyte death and mitochondrial dysfunction that lead to heart failure (HF). Reactive aldehydes such as 4-hydroxynonenal (4-HNE) are critical mediators of mitochondrial dysfunction but the sources of mitochondrial 4-HNE in cardiac diseases together with its mechanisms of action remain poorly understood. Here, we evaluated whether the mitochondrial enzyme monoamine oxidase-A (MAO-A), which generates H(2)O(2) as a by-product of catecholamine metabolism, is a source of deleterious 4-HNE in HF. We found that MAO-A activation increased mitochondrial ROS and promoted local 4-HNE production inside the mitochondria through cardiolipin peroxidation in primary cardiomyocytes. Deleterious effects of MAO-A/4-HNE on cardiac dysfunction were prevented by activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2), the main enzyme for 4-HNE metabolism. Mechanistically, MAO-A-derived 4-HNE bound to newly identified targets VDAC and MCU to promote ER-mitochondria contact sites and MCU higher-order complex formation. The resulting mitochondrial Ca(2+) accumulation participated in mitochondrial respiratory dysfunction and loss of membrane potential, as shown with the protective effects of the MCU inhibitor, RU360. Most interestingly, these findings were recapitulated in a chronic model of ischemic remodeling where pharmacological or genetic inhibition of MAO-A protected the mice from 4-HNE accumulation, MCU oligomer formation and Ca(2+) overload, thus mitigating ventricular dysfunction. To our knowledge, these are the first evidences linking MAO-A activation to mitoCa(2+) mishandling through local 4-HNE production, contributing to energetic failure and postischemic remodeling.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Chronic remodeling postmyocardial infarction consists in various maladaptive changes including interstitial fibrosis, cardiomyocyte death and mitochondrial dysfunction that lead to heart failure (HF). Reactive aldehydes such as 4-hydroxynonenal (4-HNE) are critical mediators of mitochondrial dysfunction but the sources of mitochondrial 4-HNE in cardiac diseases together with its mechanisms of action remain poorly understood. Here, we evaluated whether the mitochondrial enzyme monoamine oxidase-A (MAO-A), which generates H(2)O(2) as a by-product of catecholamine metabolism, is a source of deleterious 4-HNE in HF. We found that MAO-A activation increased mitochondrial ROS and promoted local 4-HNE production inside the mitochondria through cardiolipin peroxidation in primary cardiomyocytes. Deleterious effects of MAO-A/4-HNE on cardiac dysfunction were prevented by activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2), the main enzyme for 4-HNE metabolism. Mechanistically, MAO-A-derived 4-HNE bound to newly identified targets VDAC and MCU to promote ER-mitochondria contact sites and MCU higher-order complex formation. The resulting mitochondrial Ca(2+) accumulation participated in mitochondrial respiratory dysfunction and loss of membrane potential, as shown with the protective effects of the MCU inhibitor, RU360. Most interestingly, these findings were recapitulated in a chronic model of ischemic remodeling where pharmacological or genetic inhibition of MAO-A protected the mice from 4-HNE accumulation, MCU oligomer formation and Ca(2+) overload, thus mitigating ventricular dysfunction. To our knowledge, these are the first evidences linking MAO-A activation to mitoCa(2+) mishandling through local 4-HNE production, contributing to energetic failure and postischemic remodeling. |
Froment, Carine; Hourset, Mathilde; Sáenz-Oyhéréguy, Nancy; Mouton-Barbosa, Emmanuelle; Willmann, Claire; Zanolli, Clément; Esclassan, Rémi; Donat, Richard; è, Catherine Th; Burlet-Schiltz, Odile; Mollereau, Catherine Analysis of 5000 year-old human teeth using optimized large-scale and targeted proteomics approaches for detection of sex-specific peptides. Article de journal Journal of proteomics, 211 , p. 103548, 2020. @article{Froment2020, title = {Analysis of 5000 year-old human teeth using optimized large-scale and targeted proteomics approaches for detection of sex-specific peptides.}, author = {Carine Froment and Mathilde Hourset and Nancy Sáenz-Oyhéréguy and Emmanuelle Mouton-Barbosa and Claire Willmann and Clément Zanolli and Rémi Esclassan and Richard Donat and Catherine Th{è}ves and Odile Burlet-Schiltz and Catherine Mollereau}, doi = {10.1016/j.jprot.2019.103548}, year = {2020}, date = {2020-01-01}, journal = {Journal of proteomics}, volume = {211}, pages = {103548}, address = {Netherlands}, abstract = {The study demonstrates the high potential of MS-based proteomics coupled to an iterative database search strategy for the in-depth investigation of ancient proteomes. An efficient targeted PRM MS-based approach, although limited to the detection of a single pair of sex-specific amelogenin peptides, allowed confirming the sex of individuals in ancient dental remains, an essential information for paleoanthropologists facing the issue of sex determination and dimorphism.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The study demonstrates the high potential of MS-based proteomics coupled to an iterative database search strategy for the in-depth investigation of ancient proteomes. An efficient targeted PRM MS-based approach, although limited to the detection of a single pair of sex-specific amelogenin peptides, allowed confirming the sex of individuals in ancient dental remains, an essential information for paleoanthropologists facing the issue of sex determination and dimorphism. |
Del Corpo, Daniele ; Fullone, Maria R; Miele, Rossella; ë, Micka; Pontiggia, Daniela; Grisel, Sacha; Kieffer‐Jaquinod, Sylvie; Giardina, Thierry; Bellincampi, Daniela; Lionetti, Vincenzo Molecular Plant Pathology, p. mpp.13002, 2020, ISSN: 1464-6722, 1364-3703. @article{del_corpo_atpme17_2020, title = {AtPME17 is a functional $backslash$textitArabidopsis thaliana pectin methylesterase regulated by its PRO region that triggers PME activity in the resistance to $backslash$textitBotrytis cinerea}, author = {Daniele {Del Corpo} and Maria R Fullone and Rossella Miele and Micka{ë}l Lafond and Daniela Pontiggia and Sacha Grisel and Sylvie Kieffer‐Jaquinod and Thierry Giardina and Daniela Bellincampi and Vincenzo Lionetti}, url = {https://onlinelibrary.wiley.com/doi/10.1111/mpp.13002}, doi = {10.1111/mpp.13002}, issn = {1464-6722, 1364-3703}, year = {2020}, date = {2020-01-01}, journal = {Molecular Plant Pathology}, pages = {mpp.13002}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Farhat, Dayana C; Swale, Christopher; Dard, Céline; Cannella, Dominique; Ortet, Philippe; Barakat, Mohamed; Sindikubwabo, Fabien; Belmudes, Lucid; De Bock, Pieter-Jan ; Couté, Yohann; Bougdour, Alexandre; Hakimi, Mohamed-Ali A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment Article de journal Nature Microbiology, 2020, ISSN: 2058-5276. @article{farhat_morc-driven_2020, title = {A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment}, author = {Dayana C Farhat and Christopher Swale and Céline Dard and Dominique Cannella and Philippe Ortet and Mohamed Barakat and Fabien Sindikubwabo and Lucid Belmudes and Pieter-Jan {De Bock} and Yohann Couté and Alexandre Bougdour and Mohamed-Ali Hakimi}, url = {http://www.nature.com/articles/s41564-020-0674-4}, doi = {10.1038/s41564-020-0674-4}, issn = {2058-5276}, year = {2020}, date = {2020-01-01}, journal = {Nature Microbiology}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Di Giovanni, D; Lepetit, D; Guinet, B; Bennetot, B; Boulesteix, M; Couté, Y; Bouchez, O; Ravallec, M; Varaldi, J A behavior-manipulating virus relative as a source of adaptive genes for Drosophila parasitoids Article de journal Molecular Biology and Evolution, 2020, ISSN: 1537-1719. @article{di_giovanni_behavior-manipulating_2020, title = {A behavior-manipulating virus relative as a source of adaptive genes for Drosophila parasitoids}, author = {D {Di Giovanni} and D Lepetit and B Guinet and B Bennetot and M Boulesteix and Y Couté and O Bouchez and M Ravallec and J Varaldi}, doi = {10.1093/molbev/msaa030}, issn = {1537-1719}, year = {2020}, date = {2020-01-01}, journal = {Molecular Biology and Evolution}, abstract = {Some species of parasitic wasps have domesticated viral machineries to deliver immunosuppressive factors to their hosts. Up to now, all described cases fall into the Ichneumonoidea superfamily, which only represents around 10% of hymenoptera diversity, raising the question of whether such domestication occurred outside this clade. Furthermore, the biology of the ancestral donor viruses is completely unknown. Since the 1980's, we know that Drosophila parasitoids belonging to the Leptopilina genus, which diverged from the Ichneumonoidea superfamily 225My ago, do produce immuno-suppressive virus-like structure in their reproductive apparatus. However, the viral origin of these structures has been the subject of debate. In this paper, we provide genomic and experimental evidence that those structures do derive from an ancestral virus endogenization event. Interestingly, its close relatives induce a behaviour manipulation in present-day wasps. Thus, we conclude that virus domestication is more prevalent than previously thought and that behaviour manipulation may have been instrumental in the birth of such associations.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Some species of parasitic wasps have domesticated viral machineries to deliver immunosuppressive factors to their hosts. Up to now, all described cases fall into the Ichneumonoidea superfamily, which only represents around 10% of hymenoptera diversity, raising the question of whether such domestication occurred outside this clade. Furthermore, the biology of the ancestral donor viruses is completely unknown. Since the 1980's, we know that Drosophila parasitoids belonging to the Leptopilina genus, which diverged from the Ichneumonoidea superfamily 225My ago, do produce immuno-suppressive virus-like structure in their reproductive apparatus. However, the viral origin of these structures has been the subject of debate. In this paper, we provide genomic and experimental evidence that those structures do derive from an ancestral virus endogenization event. Interestingly, its close relatives induce a behaviour manipulation in present-day wasps. Thus, we conclude that virus domestication is more prevalent than previously thought and that behaviour manipulation may have been instrumental in the birth of such associations. |
Adhikari, Subash; Nice, Edouard C; Deutsch, Eric W; Lane, Lydie; Omenn, Gilbert S; Pennington, Stephen R; Paik, Young-Ki; Overall, Christopher M; Corrales, Fernando J; Cristea, Ileana M; Van Eyk, Jennifer E; Uhlén, Mathias; Lindskog, Cecilia; Chan, Daniel W; Bairoch, Amos; Waddington, James C; Justice, Joshua L; LaBaer, Joshua; Rodriguez, Henry; He, Fuchu; Kostrzewa, Markus; Ping, Peipei; Gundry, Rebekah L; Stewart, Peter; Srivastava, Sanjeeva; Srivastava, Sudhir; Nogueira, Fabio C S; Domont, Gilberto B; Vandenbrouck, Yves; Lam, Maggie P Y; Wennersten, Sara; Vizcaino, Juan Antonio; Wilkins, Marc; Schwenk, Jochen M; Lundberg, Emma; Bandeira, Nuno; Marko-Varga, Gyorgy; Weintraub, Susan T; Pineau, Charles; Kusebauch, Ulrike; Moritz, Robert L; Ahn, Seong Beom; Palmblad, Magnus; Snyder, Michael P; Aebersold, Ruedi; Baker, Mark S A high-stringency blueprint of the human proteome Article de journal Nature Communications, 11 (1), p. 5301, 2020, ISSN: 2041-1723. @article{adhikari_high-stringency_2020, title = {A high-stringency blueprint of the human proteome}, author = {Subash Adhikari and Edouard C Nice and Eric W Deutsch and Lydie Lane and Gilbert S Omenn and Stephen R Pennington and Young-Ki Paik and Christopher M Overall and Fernando J Corrales and Ileana M Cristea and Jennifer E {Van Eyk} and Mathias Uhlén and Cecilia Lindskog and Daniel W Chan and Amos Bairoch and James C Waddington and Joshua L Justice and Joshua LaBaer and Henry Rodriguez and Fuchu He and Markus Kostrzewa and Peipei Ping and Rebekah L Gundry and Peter Stewart and Sanjeeva Srivastava and Sudhir Srivastava and Fabio C S Nogueira and Gilberto B Domont and Yves Vandenbrouck and Maggie P Y Lam and Sara Wennersten and Juan Antonio Vizcaino and Marc Wilkins and Jochen M Schwenk and Emma Lundberg and Nuno Bandeira and Gyorgy Marko-Varga and Susan T Weintraub and Charles Pineau and Ulrike Kusebauch and Robert L Moritz and Seong Beom Ahn and Magnus Palmblad and Michael P Snyder and Ruedi Aebersold and Mark S Baker}, doi = {10.1038/s41467-020-19045-9}, issn = {2041-1723}, year = {2020}, date = {2020-01-01}, journal = {Nature Communications}, volume = {11}, number = {1}, pages = {5301}, abstract = {The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases. |
Monestier, Marie; ï, Ana; Lamboux, Aline; Cuillel, Martine; Pignot-Paintrand, Isabelle; Cassio, Doris; Charbonnier, Peggy; Um, Khémary; Harel, Amélie; Bohic, Sylvain; Gateau, Christelle; Balter, Vincent; Brun, Virginie; Delangle, Pascale; Mintz, Elisabeth A liver-targeting Cu( textlessspan style= Article de journal Metallomics, p. 10.1039.D0MT00069H, 2020, ISSN: 1756-5901, 1756-591X. @article{monestier_liver-targeting_2020, title = {A liver-targeting Cu( textlessspan style=}, author = {Marie Monestier and Ana{ï}s M Pujol and Aline Lamboux and Martine Cuillel and Isabelle Pignot-Paintrand and Doris Cassio and Peggy Charbonnier and Khémary Um and Amélie Harel and Sylvain Bohic and Christelle Gateau and Vincent Balter and Virginie Brun and Pascale Delangle and Elisabeth Mintz}, url = {http://xlink.rsc.org/?DOI=D0MT00069H}, doi = {10.1039/D0MT00069H}, issn = {1756-5901, 1756-591X}, year = {2020}, date = {2020-01-01}, journal = {Metallomics}, pages = {10.1039.D0MT00069H}, abstract = {A hepatocyte-targeting chelator promotes Cu biliary excretion, hence restoring the physiological Cu detoxification pathway in a murine Wilson's disease model. , Copper chelation is the most commonly used therapeutic strategy nowadays to treat Wilson's disease, a genetic disorder primarily inducing a pathological accumulation of Cu in the liver. The mechanism of action of Chel2, a liver-targeting Cu( i ) chelator known to promote intracellular Cu chelation, was studied in hepatic cells that reconstitute polarized epithelia with functional bile canaliculi, reminiscent of the excretion pathway in the liver. The interplay between Chel2 and Cu localization in these cells was demonstrated through confocal microscopy using a fluorescent derivative and nano X-ray fluorescence. The Cu( i ) bound chelator was found in vesicles potentially excreted in the canaliculi. Moreover, injection of Chel2 either intravenously or subcutaneously to a murine model of Wilson's disease increased excretion of Cu in the faeces, confirming in vivo biliary excretion. Therefore, Chel2 turns out to be a possible means to collect and excrete hepatic Cu in the faeces, hence restoring the physiological pathway.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A hepatocyte-targeting chelator promotes Cu biliary excretion, hence restoring the physiological Cu detoxification pathway in a murine Wilson's disease model. , Copper chelation is the most commonly used therapeutic strategy nowadays to treat Wilson's disease, a genetic disorder primarily inducing a pathological accumulation of Cu in the liver. The mechanism of action of Chel2, a liver-targeting Cu( i ) chelator known to promote intracellular Cu chelation, was studied in hepatic cells that reconstitute polarized epithelia with functional bile canaliculi, reminiscent of the excretion pathway in the liver. The interplay between Chel2 and Cu localization in these cells was demonstrated through confocal microscopy using a fluorescent derivative and nano X-ray fluorescence. The Cu( i ) bound chelator was found in vesicles potentially excreted in the canaliculi. Moreover, injection of Chel2 either intravenously or subcutaneously to a murine model of Wilson's disease increased excretion of Cu in the faeces, confirming in vivo biliary excretion. Therefore, Chel2 turns out to be a possible means to collect and excrete hepatic Cu in the faeces, hence restoring the physiological pathway. |
Van Gool, Alain ; Corrales, Fernado; ć, Mirjana {Č}olovi; ć, Danijela Krsti; Oliver-Martos, Begona; Martínez-Cáceres, Eva; Jakasa, Ivone; Gajski, Goran; Brun, Virginie; Kyriacou, Kyriacos; Burzynska-Pedziwiatr, Izabela; Wozniak, Lucyna Alicja; Nierkens, Stephan; Pascual García, César ; Katrlik, Jaroslav; Bojic-Trbojevic, Zanka; Vacek, Jan; Llorente, Alicia; Antohe, Felicia; Suica, Viorel; Suarez, Guillaume; T'Kindt, Ruben; Martin, Petra; Penque, Deborah; Martins, Ines Lanca; Bodoki, Ede; Iacob, Bogdan-Cezar; Aydindogan, Eda; Timur, Suna; Allinson, John; Sutton, Christopher; Luider, Theo; Wittfooth, Saara; Sammar, Marei Analytical techniques for multiplex analysis of protein biomarkers Article de journal Expert Review of Proteomics, p. 1–17, 2020, ISSN: 1744-8387. @article{van_gool_analytical_2020, title = {Analytical techniques for multiplex analysis of protein biomarkers}, author = {Alain {Van Gool} and Fernado Corrales and Mirjana {Č}olovi{ć} and Danijela Krsti{ć} and Begona Oliver-Martos and Eva Martínez-Cáceres and Ivone Jakasa and Goran Gajski and Virginie Brun and Kyriacos Kyriacou and Izabela Burzynska-Pedziwiatr and Lucyna Alicja Wozniak and Stephan Nierkens and César {Pascual García} and Jaroslav Katrlik and Zanka Bojic-Trbojevic and Jan Vacek and Alicia Llorente and Felicia Antohe and Viorel Suica and Guillaume Suarez and Ruben T'Kindt and Petra Martin and Deborah Penque and Ines Lanca Martins and Ede Bodoki and Bogdan-Cezar Iacob and Eda Aydindogan and Suna Timur and John Allinson and Christopher Sutton and Theo Luider and Saara Wittfooth and Marei Sammar}, doi = {10.1080/14789450.2020.1763174}, issn = {1744-8387}, year = {2020}, date = {2020-01-01}, journal = {Expert Review of Proteomics}, pages = {1--17}, abstract = {INTRODUCTION: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. AREAS COVERED: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. EXPERT COMMENTARY: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine.}, keywords = {}, pubstate = {published}, tppubtype = {article} } INTRODUCTION: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. AREAS COVERED: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. EXPERT COMMENTARY: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine. |
Couté, Yohann; Bruley, Christophe; Burger, Thomas Beyond target-decoy competition: stable validation of peptide and protein identifications in mass spectrometry-based discovery proteomics Article de journal Analytical Chemistry, 2020, ISSN: 1520-6882. @article{coute_beyond_2020, title = {Beyond target-decoy competition: stable validation of peptide and protein identifications in mass spectrometry-based discovery proteomics}, author = {Yohann Couté and Christophe Bruley and Thomas Burger}, doi = {10.1021/acs.analchem.0c00328}, issn = {1520-6882}, year = {2020}, date = {2020-01-01}, journal = {Analytical Chemistry}, abstract = {In bottom-up discovery proteomics, target-decoy competition (TDC) is the most popular method for false discovery rate (FDR) control. Despite unquestionable statistical foundations, this method has drawbacks, including its hitherto unknown intrinsic lack of stability vis-à-vis practical conditions of application. Although some consequences of this instability have already been empirically described, they may have been misinterpreted. This article provides evidence that TDC has become less reliable as the accuracy of modern mass spectrometers improved. We therefore propose to replace TDC by a totally different method to control the FDR at spectrum, peptide and protein levels, while benefiting from the theoretical guarantees of the Benjamini-Hochberg framework. As this method is simpler to use, faster to compute and more stable than TDC, we argue that it is better adapted to the standardization and throughput constraints of current proteomic platforms.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In bottom-up discovery proteomics, target-decoy competition (TDC) is the most popular method for false discovery rate (FDR) control. Despite unquestionable statistical foundations, this method has drawbacks, including its hitherto unknown intrinsic lack of stability vis-à-vis practical conditions of application. Although some consequences of this instability have already been empirically described, they may have been misinterpreted. This article provides evidence that TDC has become less reliable as the accuracy of modern mass spectrometers improved. We therefore propose to replace TDC by a totally different method to control the FDR at spectrum, peptide and protein levels, while benefiting from the theoretical guarantees of the Benjamini-Hochberg framework. As this method is simpler to use, faster to compute and more stable than TDC, we argue that it is better adapted to the standardization and throughput constraints of current proteomic platforms. |
Lacombe, Maud; Jaquinod, Michel; Belmudes, Lucid; Couté, Yohann; Ramus, Claire; Combes, Florence; Burger, Thomas; Mintz, Elisabeth; Barthelon, Justine; Leroy, Vincent; Poujois, Aurélia; Lachaux, Alain; Woimant, France; Brun, Virginie Comprehensive and comparative exploration of the $backslash$textitAtp7b $^backslashtextrm−/−$ mouse plasma proteome Article de journal Metallomics, p. 10.1039.C9MT00225A, 2020, ISSN: 1756-5901, 1756-591X. @article{lacombe_comprehensive_2020, title = {Comprehensive and comparative exploration of the $backslash$textitAtp7b $^backslashtextrm−/−$ mouse plasma proteome}, author = {Maud Lacombe and Michel Jaquinod and Lucid Belmudes and Yohann Couté and Claire Ramus and Florence Combes and Thomas Burger and Elisabeth Mintz and Justine Barthelon and Vincent Leroy and Aurélia Poujois and Alain Lachaux and France Woimant and Virginie Brun}, url = {http://xlink.rsc.org/?DOI=C9MT00225A}, doi = {10.1039/C9MT00225A}, issn = {1756-5901, 1756-591X}, year = {2020}, date = {2020-01-01}, journal = {Metallomics}, pages = {10.1039.C9MT00225A}, abstract = {Wilson's disease (WD) is a rare genetic disease caused by mutations in the ATP7B gene. In this study, we used MS-based proteomics to explore the plasma proteome of the Atp7b −/− mouse, a genetic and phenotypic model for WD. , Wilson's disease (WD), a rare genetic disease caused by mutations in the ATP7B gene, is associated with altered expression and/or function of the copper-transporting ATP7B protein, leading to massive toxic accumulation of copper in the liver and brain. The Atp7b −/− mouse, a genetic and phenotypic model of WD, was developed to provide new insights into the pathogenic mechanisms of WD. Many plasma proteins are secreted by the liver, and impairment of liver function can trigger changes to the plasma proteome. High standard proteomics workflows can identify such changes. Here, we explored the plasma proteome of the Atp7b −/− mouse using a mass spectrometry (MS)-based proteomics workflow combining unbiased discovery analysis followed by targeted quantification. Among the 367 unique plasma proteins identified, 7 proteins were confirmed as differentially abundant between Atp7b −/− mice and wild-type littermates, and were directly linked to WD pathophysiology (regeneration of liver parenchyma, plasma iron depletion, etc. ). We then adapted our targeted proteomics assay to quantify human orthologues of these proteins in plasma from copper-chelator-treated WD patients. The plasma proteome changes observed in the Atp7b −/− mouse were not confirmed in these samples, except for alpha-1 antichymotrypsin, levels of which were decreased in WD patients compared to healthy individuals. Plasma ceruloplasmin was investigated in both the Atp7b −/− mouse model and human patients; it was significantly decreased in the human form of WD only. In conclusion, MS-based proteomics is a method of choice to identify proteome changes in murine models of disrupted metal homeostasis, and allows their validation in human cohorts.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Wilson's disease (WD) is a rare genetic disease caused by mutations in the ATP7B gene. In this study, we used MS-based proteomics to explore the plasma proteome of the Atp7b −/− mouse, a genetic and phenotypic model for WD. , Wilson's disease (WD), a rare genetic disease caused by mutations in the ATP7B gene, is associated with altered expression and/or function of the copper-transporting ATP7B protein, leading to massive toxic accumulation of copper in the liver and brain. The Atp7b −/− mouse, a genetic and phenotypic model of WD, was developed to provide new insights into the pathogenic mechanisms of WD. Many plasma proteins are secreted by the liver, and impairment of liver function can trigger changes to the plasma proteome. High standard proteomics workflows can identify such changes. Here, we explored the plasma proteome of the Atp7b −/− mouse using a mass spectrometry (MS)-based proteomics workflow combining unbiased discovery analysis followed by targeted quantification. Among the 367 unique plasma proteins identified, 7 proteins were confirmed as differentially abundant between Atp7b −/− mice and wild-type littermates, and were directly linked to WD pathophysiology (regeneration of liver parenchyma, plasma iron depletion, etc. ). We then adapted our targeted proteomics assay to quantify human orthologues of these proteins in plasma from copper-chelator-treated WD patients. The plasma proteome changes observed in the Atp7b −/− mouse were not confirmed in these samples, except for alpha-1 antichymotrypsin, levels of which were decreased in WD patients compared to healthy individuals. Plasma ceruloplasmin was investigated in both the Atp7b −/− mouse model and human patients; it was significantly decreased in the human form of WD only. In conclusion, MS-based proteomics is a method of choice to identify proteome changes in murine models of disrupted metal homeostasis, and allows their validation in human cohorts. |
Jeudy, Sandra; Bertaux, Lionel; Alempic, Jean-Marie; Lartigue, Audrey; Legendre, Matthieu; Belmudes, Lucid; Santini, Sébastien; è, Nad; Beucher, Laure; Biondi, Emanuele G; Juul, Sissel; Turner, Daniel J; Couté, Yohann; Claverie, Jean-Michel; Abergel, Chantal Exploration of the propagation of transpovirons within Mimiviridae reveals a unique example of commensalism in the viral world Article de journal The ISME journal, 14 (3), p. 727–739, 2020, ISSN: 1751-7370. @article{jeudy_exploration_2020, title = {Exploration of the propagation of transpovirons within Mimiviridae reveals a unique example of commensalism in the viral world}, author = {Sandra Jeudy and Lionel Bertaux and Jean-Marie Alempic and Audrey Lartigue and Matthieu Legendre and Lucid Belmudes and Sébastien Santini and Nad{è}ge Philippe and Laure Beucher and Emanuele G Biondi and Sissel Juul and Daniel J Turner and Yohann Couté and Jean-Michel Claverie and Chantal Abergel}, doi = {10.1038/s41396-019-0565-y}, issn = {1751-7370}, year = {2020}, date = {2020-01-01}, journal = {The ISME journal}, volume = {14}, number = {3}, pages = {727--739}, abstract = {Acanthamoeba-infecting Mimiviridae are giant viruses with dsDNA genome up to 1.5 Mb. They build viral factories in the host cytoplasm in which the nuclear-like virus-encoded functions take place. They are themselves the target of infections by 20-kb-dsDNA virophages, replicating in the giant virus factories and can also be found associated with 7-kb-DNA episomes, dubbed transpovirons. Here we isolated a virophage (Zamilon vitis) and two transpovirons respectively associated to B- and C-clade mimiviruses. We found that the virophage could transfer each transpoviron provided the host viruses were devoid of a resident transpoviron (permissive effect). If not, only the resident transpoviron originally isolated from the corresponding virus was replicated and propagated within the virophage progeny (dominance effect). Although B- and C-clade viruses devoid of transpoviron could replicate each transpoviron, they did it with a lower efficiency across clades, suggesting an ongoing process of adaptive co-evolution. We analysed the proteomes of host viruses and virophage particles in search of proteins involved in this adaptation process. This study also highlights a unique example of intricate commensalism in the viral world, where the transpoviron uses the virophage to propagate and where the Zamilon virophage and the transpoviron depend on the giant virus to replicate, without affecting its infectious cycle.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Acanthamoeba-infecting Mimiviridae are giant viruses with dsDNA genome up to 1.5 Mb. They build viral factories in the host cytoplasm in which the nuclear-like virus-encoded functions take place. They are themselves the target of infections by 20-kb-dsDNA virophages, replicating in the giant virus factories and can also be found associated with 7-kb-DNA episomes, dubbed transpovirons. Here we isolated a virophage (Zamilon vitis) and two transpovirons respectively associated to B- and C-clade mimiviruses. We found that the virophage could transfer each transpoviron provided the host viruses were devoid of a resident transpoviron (permissive effect). If not, only the resident transpoviron originally isolated from the corresponding virus was replicated and propagated within the virophage progeny (dominance effect). Although B- and C-clade viruses devoid of transpoviron could replicate each transpoviron, they did it with a lower efficiency across clades, suggesting an ongoing process of adaptive co-evolution. We analysed the proteomes of host viruses and virophage particles in search of proteins involved in this adaptation process. This study also highlights a unique example of intricate commensalism in the viral world, where the transpoviron uses the virophage to propagate and where the Zamilon virophage and the transpoviron depend on the giant virus to replicate, without affecting its infectious cycle. |
Nguyen, Minh Vu Chuong; ï, Ana; Adrait, Annie; Defendi, Federica; Couté, Yohann; Baillet, Athan; Guigue, Lisa; Gottenberg, Jacques-Eric; Dumestre-Pérard, Chantal; Brun, Virginie; Gaudin, Philippe Fetuin-A and thyroxin binding globulin predict rituximab response in rheumatoid arthritis patients with insufficient response to anti-TNF$alpha$ Article de journal Clinical Rheumatology, 2020, ISSN: 1434-9949. @article{nguyen_fetuin-and_2020, title = {Fetuin-A and thyroxin binding globulin predict rituximab response in rheumatoid arthritis patients with insufficient response to anti-TNF$alpha$}, author = {Minh Vu Chuong Nguyen and Ana{ï}s Courtier and Annie Adrait and Federica Defendi and Yohann Couté and Athan Baillet and Lisa Guigue and Jacques-Eric Gottenberg and Chantal Dumestre-Pérard and Virginie Brun and Philippe Gaudin}, doi = {10.1007/s10067-020-05030-6}, issn = {1434-9949}, year = {2020}, date = {2020-01-01}, journal = {Clinical Rheumatology}, abstract = {OBJECTIVES: Rheumatoid arthritis (RA) is a debilitating disease, but patient management and treatment have been revolutionized since the advent of bDMARDs. However, about one third of RA patients do not respond to specific bDMARD treatment without clear identified reasons. Different bDMARDs must be tried until the right drug is found. Here, we sought to identify a predictive protein signature to stratify patient responsiveness to rituximab (RTX) among patients with an insufficient response to a first anti-TNF$alpha$ treatment. METHODS: Serum samples were collected at baseline before RTX initiation. A proteomics study comparing responders and nonresponders was conducted to identify and select potential predictive biomarkers whose concentration was measured by quantitative assays. Logistic regression was performed to determine the best biomarker combination to predict good or nonresponse to RTX (EULAR criteria after 6 months' treatment). RESULTS: Eleven biomarkers potentially discriminating between responders and nonresponders were selected following discovery proteomics. Quantitative immunoassays and univariate statistical analysis showed that fetuin-A and thyroxine binding globulin (TBG) presented a good capacity to discriminate between patient groups. A logistic regression analysis revealed that the combination of fetuin-A plus TBG could accurately predict a patient's responsiveness to RTX with an AUC of 0.86, sensitivity of 80%, and a specificity of 79%. CONCLUSION: In RA patients for whom a first anti-TNF$alpha$ treatment has failed, the serum abundance of fetuin-A and TBG before initiating RTX treatment is an indicator for their response status at 6 months. ClinicalTrials.gov identifier: NCT01000441.Key Points• Proteomic analysis revealed 11 putative predictive biomarkers to discriminate rituximab responder vs. nonresponder RA patients.• Fetuin-A and TBG are significantly differentially expressed at baseline in rituximab responder vs. nonresponder RA patients.• Algorithm combining fetuin-A and TBG accurately predicts response to rituximab in RA patients with insufficient response to TNFi.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVES: Rheumatoid arthritis (RA) is a debilitating disease, but patient management and treatment have been revolutionized since the advent of bDMARDs. However, about one third of RA patients do not respond to specific bDMARD treatment without clear identified reasons. Different bDMARDs must be tried until the right drug is found. Here, we sought to identify a predictive protein signature to stratify patient responsiveness to rituximab (RTX) among patients with an insufficient response to a first anti-TNF$alpha$ treatment. METHODS: Serum samples were collected at baseline before RTX initiation. A proteomics study comparing responders and nonresponders was conducted to identify and select potential predictive biomarkers whose concentration was measured by quantitative assays. Logistic regression was performed to determine the best biomarker combination to predict good or nonresponse to RTX (EULAR criteria after 6 months' treatment). RESULTS: Eleven biomarkers potentially discriminating between responders and nonresponders were selected following discovery proteomics. Quantitative immunoassays and univariate statistical analysis showed that fetuin-A and thyroxine binding globulin (TBG) presented a good capacity to discriminate between patient groups. A logistic regression analysis revealed that the combination of fetuin-A plus TBG could accurately predict a patient's responsiveness to RTX with an AUC of 0.86, sensitivity of 80%, and a specificity of 79%. CONCLUSION: In RA patients for whom a first anti-TNF$alpha$ treatment has failed, the serum abundance of fetuin-A and TBG before initiating RTX treatment is an indicator for their response status at 6 months. ClinicalTrials.gov identifier: NCT01000441.Key Points• Proteomic analysis revealed 11 putative predictive biomarkers to discriminate rituximab responder vs. nonresponder RA patients.• Fetuin-A and TBG are significantly differentially expressed at baseline in rituximab responder vs. nonresponder RA patients.• Algorithm combining fetuin-A and TBG accurately predicts response to rituximab in RA patients with insufficient response to TNFi. |
è, Hél; ï, Hélo; Vegna, Serena; Lahlali, Thomas; Pons, Caroline; Michelet, Maud; Couté, Yohann; Belmudes, Lucid; Chadeuf, Gilliane; Kim, Yujin; Di Bernardo, Ariel ; Jalaguier, Pascal; ï, Fran{ç}ois-Lo; Fusil, Floriane; Rivoire, Michel; Arnold, Lee D; Lopatin, Uri; Combet, Christophe; Zoulim, Fabien; Grierson, David; Chabot, Benoit; Lucifora, Julie; Durantel, David; Salvetti, Anna Hepatitis B virus Core protein nuclear interactome identifies SRSF10 as a host RNA-binding protein restricting HBV RNA production Article de journal PLoS pathogens, 16 (11), p. e1008593, 2020, ISSN: 1553-7374. @article{chabrolles_hepatitis_2020, title = {Hepatitis B virus Core protein nuclear interactome identifies SRSF10 as a host RNA-binding protein restricting HBV RNA production}, author = {Hél{è}ne Chabrolles and Hélo{ï}se Auclair and Serena Vegna and Thomas Lahlali and Caroline Pons and Maud Michelet and Yohann Couté and Lucid Belmudes and Gilliane Chadeuf and Yujin Kim and Ariel {Di Bernardo} and Pascal Jalaguier and Fran{ç}ois-Lo{ï}c Cosset and Floriane Fusil and Michel Rivoire and Lee D Arnold and Uri Lopatin and Christophe Combet and Fabien Zoulim and David Grierson and Benoit Chabot and Julie Lucifora and David Durantel and Anna Salvetti}, doi = {10.1371/journal.ppat.1008593}, issn = {1553-7374}, year = {2020}, date = {2020-01-01}, journal = {PLoS pathogens}, volume = {16}, number = {11}, pages = {e1008593}, abstract = {Despite the existence of a preventive vaccine, chronic infection with Hepatitis B virus (HBV) affects more than 250 million people and represents a major global cause of hepatocellular carcinoma (HCC) worldwide. Current clinical treatments, in most of cases, do not eliminate viral genome that persists as a DNA episome in the nucleus of hepatocytes and constitutes a stable template for the continuous expression of viral genes. Several studies suggest that, among viral factors, the HBV core protein (HBc), well-known for its structural role in the cytoplasm, could have critical regulatory functions in the nucleus of infected hepatocytes. To elucidate these functions, we performed a proteomic analysis of HBc-interacting host-factors in the nucleus of differentiated HepaRG, a surrogate model of human hepatocytes. The HBc interactome was found to consist primarily of RNA-binding proteins (RBPs), which are involved in various aspects of mRNA metabolism. Among them, we focused our studies on SRSF10, a RBP that was previously shown to regulate alternative splicing (AS) in a phosphorylation-dependent manner and to control stress and DNA damage responses, as well as viral replication. Functional studies combining SRSF10 knockdown and a pharmacological inhibitor of SRSF10 phosphorylation (1C8) showed that SRSF10 behaves as a restriction factor that regulates HBV RNAs levels and that its dephosphorylated form is likely responsible for the anti-viral effect. Surprisingly, neither SRSF10 knock-down nor 1C8 treatment modified the splicing of HBV RNAs but rather modulated the level of nascent HBV RNA. Altogether, our work suggests that in the nucleus of infected cells HBc interacts with multiple RBPs that regulate viral RNA metabolism. Our identification of SRSF10 as a new anti-HBV restriction factor offers new perspectives for the development of new host-targeted antiviral strategies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Despite the existence of a preventive vaccine, chronic infection with Hepatitis B virus (HBV) affects more than 250 million people and represents a major global cause of hepatocellular carcinoma (HCC) worldwide. Current clinical treatments, in most of cases, do not eliminate viral genome that persists as a DNA episome in the nucleus of hepatocytes and constitutes a stable template for the continuous expression of viral genes. Several studies suggest that, among viral factors, the HBV core protein (HBc), well-known for its structural role in the cytoplasm, could have critical regulatory functions in the nucleus of infected hepatocytes. To elucidate these functions, we performed a proteomic analysis of HBc-interacting host-factors in the nucleus of differentiated HepaRG, a surrogate model of human hepatocytes. The HBc interactome was found to consist primarily of RNA-binding proteins (RBPs), which are involved in various aspects of mRNA metabolism. Among them, we focused our studies on SRSF10, a RBP that was previously shown to regulate alternative splicing (AS) in a phosphorylation-dependent manner and to control stress and DNA damage responses, as well as viral replication. Functional studies combining SRSF10 knockdown and a pharmacological inhibitor of SRSF10 phosphorylation (1C8) showed that SRSF10 behaves as a restriction factor that regulates HBV RNAs levels and that its dephosphorylated form is likely responsible for the anti-viral effect. Surprisingly, neither SRSF10 knock-down nor 1C8 treatment modified the splicing of HBV RNAs but rather modulated the level of nascent HBV RNA. Altogether, our work suggests that in the nucleus of infected cells HBc interacts with multiple RBPs that regulate viral RNA metabolism. Our identification of SRSF10 as a new anti-HBV restriction factor offers new perspectives for the development of new host-targeted antiviral strategies. |
van Lis, Robert; è, Sabine Brugi; Baffert, Carole; Couté, Yohann; Nitschke, Wolfgang; Atteia, Ariane Hybrid cluster proteins in a photosynthetic microalga Article de journal The FEBS journal, 287 (4), p. 721–735, 2020, ISSN: 1742-4658. @article{van_lis_hybrid_2020, title = {Hybrid cluster proteins in a photosynthetic microalga}, author = {Robert van Lis and Sabine Brugi{è}re and Carole Baffert and Yohann Couté and Wolfgang Nitschke and Ariane Atteia}, doi = {10.1111/febs.15025}, issn = {1742-4658}, year = {2020}, date = {2020-01-01}, journal = {The FEBS journal}, volume = {287}, number = {4}, pages = {721--735}, abstract = {Hybrid cluster proteins (HCPs) are metalloproteins characterized by the presence of an iron-sulfur-oxygen cluster. These proteins occur in all three domains of life. In eukaryotes, HCPs have so far been found only in a few anaerobic parasites and photosynthetic microalgae. With respect to all species harboring an HCP, the green microalga Chlamydomonas reinhardtii stands out by the presence of four HCP genes. The study of the gene and protein structures as well as the phylogenetic analyses strongly support a model in which the HCP family in the alga has emerged from a single gene of alpha proteobacterial origin and then expanded by several rounds of duplications. The spectra and redox properties of HCP1 and HCP3, produced heterologously in Escherichia coli, were analyzed by electron paramagnetic resonance spectroscopy on redox-titrated samples. Both proteins contain a [4Fe-4S]-cluster as well as a [4Fe-2O-2S]-hybrid cluster with paramagnetic properties related to those of HCPs from Desulfovibrio species. Immunoblotting experiments combined with mass spectrometry-based proteomics showed that both nitrate and darkness contribute to the strong upregulation of the HCP levels in C. reinhardtii growing under oxic conditions. The link to the nitrate metabolism is discussed in the light of recent data on the potential role of HCP in S-nitrosylation in bacteria.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Hybrid cluster proteins (HCPs) are metalloproteins characterized by the presence of an iron-sulfur-oxygen cluster. These proteins occur in all three domains of life. In eukaryotes, HCPs have so far been found only in a few anaerobic parasites and photosynthetic microalgae. With respect to all species harboring an HCP, the green microalga Chlamydomonas reinhardtii stands out by the presence of four HCP genes. The study of the gene and protein structures as well as the phylogenetic analyses strongly support a model in which the HCP family in the alga has emerged from a single gene of alpha proteobacterial origin and then expanded by several rounds of duplications. The spectra and redox properties of HCP1 and HCP3, produced heterologously in Escherichia coli, were analyzed by electron paramagnetic resonance spectroscopy on redox-titrated samples. Both proteins contain a [4Fe-4S]-cluster as well as a [4Fe-2O-2S]-hybrid cluster with paramagnetic properties related to those of HCPs from Desulfovibrio species. Immunoblotting experiments combined with mass spectrometry-based proteomics showed that both nitrate and darkness contribute to the strong upregulation of the HCP levels in C. reinhardtii growing under oxic conditions. The link to the nitrate metabolism is discussed in the light of recent data on the potential role of HCP in S-nitrosylation in bacteria. |
Adrait, Annie; Dumonceau, Jean-Marc; Delhaye, Myriam; Annessi-Ramseyer, Isabelle; Frossard, Jean-Louis; Coute, Yohann; Farina, Annarita Liquid Biopsy of Bile based on Targeted Mass Spectrometry for the Diagnosis of Malignant Biliary Strictures Article de journal Clinical and Translational Science, 2020, ISSN: 1752-8062. @article{adrait_liquid_2020, title = {Liquid Biopsy of Bile based on Targeted Mass Spectrometry for the Diagnosis of Malignant Biliary Strictures}, author = {Annie Adrait and Jean-Marc Dumonceau and Myriam Delhaye and Isabelle Annessi-Ramseyer and Jean-Louis Frossard and Yohann Coute and Annarita Farina}, doi = {10.1111/cts.12890}, issn = {1752-8062}, year = {2020}, date = {2020-01-01}, journal = {Clinical and Translational Science}, abstract = {Bile holds biomarkers of malignant biliary strictures (MBS) but is unsuited for automated analyzers used in routine diagnostic laboratories. Selected Reaction Monitoring (SRM) is a flexible high-throughput analytical approach based on targeted mass spectrometry (MS) already implemented in clinical settings. We tested the hypothesis that SRM could be used to quantify cancer biomarkers in human bile. An SRM-based assay was developed to simultaneously quantify up to 37 peptides from 13 bile proteins in a developmental cohort of 15 patients (MBS}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bile holds biomarkers of malignant biliary strictures (MBS) but is unsuited for automated analyzers used in routine diagnostic laboratories. Selected Reaction Monitoring (SRM) is a flexible high-throughput analytical approach based on targeted mass spectrometry (MS) already implemented in clinical settings. We tested the hypothesis that SRM could be used to quantify cancer biomarkers in human bile. An SRM-based assay was developed to simultaneously quantify up to 37 peptides from 13 bile proteins in a developmental cohort of 15 patients (MBS |
Couté, Yohann; Kraut, Alexandra; Zimmermann, Christine; Büscher, Nicole; Hesse, Anne-Marie; Bruley, Christophe; De Andrea, Marco ; Wangen, Christina; Hahn, Friedrich; Marschall, Manfred; Plachter, Bodo Mass Spectrometry-Based Characterization of the Virion Proteome, Phosphoproteome, and Associated Kinase Activity of Human Cytomegalovirus Article de journal Microorganisms, 8 (6), p. 820, 2020, ISSN: 2076-2607. @article{coute_mass_2020, title = {Mass Spectrometry-Based Characterization of the Virion Proteome, Phosphoproteome, and Associated Kinase Activity of Human Cytomegalovirus}, author = {Yohann Couté and Alexandra Kraut and Christine Zimmermann and Nicole Büscher and Anne-Marie Hesse and Christophe Bruley and Marco {De Andrea} and Christina Wangen and Friedrich Hahn and Manfred Marschall and Bodo Plachter}, url = {https://www.mdpi.com/2076-2607/8/6/820}, doi = {10.3390/microorganisms8060820}, issn = {2076-2607}, year = {2020}, date = {2020-01-01}, journal = {Microorganisms}, volume = {8}, number = {6}, pages = {820}, abstract = {The assembly of human cytomegalovirus (HCMV) virions is an orchestrated process that requires, as an essential prerequisite, the complex crosstalk between viral structural proteins. Currently, however, the mechanisms governing the successive steps in the constitution of virion protein complexes remain elusive. Protein phosphorylation is a key regulator determining the sequential changes in the conformation, binding, dynamics, and stability of proteins in the course of multiprotein assembly. In this review, we present a comprehensive map of the HCMV virion proteome, including a refined view on the virion phosphoproteome, based on previous publications supplemented by new results. Thus, a novel dataset of viral and cellular proteins contained in HCMV virions is generated, providing a basis for future analyses of individual phosphorylation steps and sites involved in the orchestrated assembly of HCMV virion-specific multiprotein complexes. Finally, we present the current knowledge on the activity of pUL97, the HCMV-encoded and virion-associated kinase, in phosphorylating viral and host proteins.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The assembly of human cytomegalovirus (HCMV) virions is an orchestrated process that requires, as an essential prerequisite, the complex crosstalk between viral structural proteins. Currently, however, the mechanisms governing the successive steps in the constitution of virion protein complexes remain elusive. Protein phosphorylation is a key regulator determining the sequential changes in the conformation, binding, dynamics, and stability of proteins in the course of multiprotein assembly. In this review, we present a comprehensive map of the HCMV virion proteome, including a refined view on the virion phosphoproteome, based on previous publications supplemented by new results. Thus, a novel dataset of viral and cellular proteins contained in HCMV virions is generated, providing a basis for future analyses of individual phosphorylation steps and sites involved in the orchestrated assembly of HCMV virion-specific multiprotein complexes. Finally, we present the current knowledge on the activity of pUL97, the HCMV-encoded and virion-associated kinase, in phosphorylating viral and host proteins. |
Crespo, Marion; Damont, Annelaure; Blanco, Melina; Lastrucci, Emmanuelle; Kennani, Sara El; ô, C; Khattabi, Laila El; Terrier, Samuel; Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Hesse, Anne-Marie; Bruley, Christophe; Chantalat, Sophie; ô, Jér; ç, Fran; Battail, Christophe; Cocquet, Julie; Pflieger, Delphine Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes Article de journal Nucleic Acids Research, 48 (8), p. 4115–4138, 2020, ISSN: 0305-1048, 1362-4962. @article{crespo_multi-omic_2020, title = {Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes}, author = {Marion Crespo and Annelaure Damont and Melina Blanco and Emmanuelle Lastrucci and Sara El Kennani and C{ô}me Ialy-Radio and Laila El Khattabi and Samuel Terrier and Mathilde Louwagie and Sylvie Kieffer-Jaquinod and Anne-Marie Hesse and Christophe Bruley and Sophie Chantalat and Jér{ô}me Govin and Fran{ç}ois Fenaille and Christophe Battail and Julie Cocquet and Delphine Pflieger}, url = {https://academic.oup.com/nar/article/48/8/4115/5809165}, doi = {10.1093/nar/gkaa163}, issn = {0305-1048, 1362-4962}, year = {2020}, date = {2020-01-01}, journal = {Nucleic Acids Research}, volume = {48}, number = {8}, pages = {4115--4138}, abstract = {Abstract Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification. |
Kloehn, Joachim; Oppenheim, Rebecca D; Siddiqui, Ghizal; De Bock, Pieter-Jan ; Kumar Dogga, Sunil ; Coute, Yohann; Hakimi, Mohamed-Ali; Creek, Darren J; Soldati-Favre, Dominique Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii Article de journal BMC Biology, 18 (1), p. 67, 2020, ISSN: 1741-7007. @article{kloehn_multi-omics_2020, title = {Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii}, author = {Joachim Kloehn and Rebecca D Oppenheim and Ghizal Siddiqui and Pieter-Jan {De Bock} and Sunil {Kumar Dogga} and Yohann Coute and Mohamed-Ali Hakimi and Darren J Creek and Dominique Soldati-Favre}, url = {https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-020-00791-7}, doi = {10.1186/s12915-020-00791-7}, issn = {1741-7007}, year = {2020}, date = {2020-01-01}, journal = {BMC Biology}, volume = {18}, number = {1}, pages = {67}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Sansa, Marc; Defoort, Martial; Brenac, Ariel; Hermouet, Maxime; Banniard, Louise; Fafin, Alexandre; Gely, Marc; Masselon, Christophe; Favero, Ivan; Jourdan, Guillaume; Hentz, Sébastien Optomechanical mass spectrometry Article de journal Nature Communications, 11 (1), p. 3781, 2020, ISSN: 2041-1723. @article{sansa_optomechanical_2020, title = {Optomechanical mass spectrometry}, author = {Marc Sansa and Martial Defoort and Ariel Brenac and Maxime Hermouet and Louise Banniard and Alexandre Fafin and Marc Gely and Christophe Masselon and Ivan Favero and Guillaume Jourdan and Sébastien Hentz}, doi = {10.1038/s41467-020-17592-9}, issn = {2041-1723}, year = {2020}, date = {2020-01-01}, journal = {Nature Communications}, volume = {11}, number = {1}, pages = {3781}, abstract = {Nanomechanical mass spectrometry has proven to be well suited for the analysis of high mass species such as viruses. Still, the use of one-dimensional devices such as vibrating beams forces a trade-off between analysis time and mass resolution. Complex readout schemes are also required to simultaneously monitor multiple resonance modes, which degrades resolution. These issues restrict nanomechanical MS to specific species. We demonstrate here single-particle mass spectrometry with nano-optomechanical resonators fabricated with a Very Large Scale Integration process. The unique motion sensitivity of optomechanics allows designs that are impervious to particle position, stiffness or shape, opening the way to the analysis of large aspect ratio biological objects of great significance such as viruses with a tail or fibrils. Compared to top-down beam resonators with electrical read-out and state-of-the-art mass resolution, we show a three-fold improvement in capture area with no resolution degradation, despite the use of a single resonance mode.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Nanomechanical mass spectrometry has proven to be well suited for the analysis of high mass species such as viruses. Still, the use of one-dimensional devices such as vibrating beams forces a trade-off between analysis time and mass resolution. Complex readout schemes are also required to simultaneously monitor multiple resonance modes, which degrades resolution. These issues restrict nanomechanical MS to specific species. We demonstrate here single-particle mass spectrometry with nano-optomechanical resonators fabricated with a Very Large Scale Integration process. The unique motion sensitivity of optomechanics allows designs that are impervious to particle position, stiffness or shape, opening the way to the analysis of large aspect ratio biological objects of great significance such as viruses with a tail or fibrils. Compared to top-down beam resonators with electrical read-out and state-of-the-art mass resolution, we show a three-fold improvement in capture area with no resolution degradation, despite the use of a single resonance mode. |
Postic, Guillaume; Marcoux, Julien; Reys, Victor; Andreani, Jessica; Vandenbrouck, Yves; Bousquet, Marie-Pierre; Mouton-Barbosa, Emmanuelle; Cianférani, Sarah; Burlet-Schiltz, Odile; Guerois, Raphael; Labesse, Gilles; Tufféry, Pierre Probing Protein Interaction Networks by Combining MS-Based Proteomics and Structural Data Integration. Article de journal Journal of proteome research, 19 (7), p. 2807–2820, 2020. @article{Postic2020, title = {Probing Protein Interaction Networks by Combining MS-Based Proteomics and Structural Data Integration.}, author = {Guillaume Postic and Julien Marcoux and Victor Reys and Jessica Andreani and Yves Vandenbrouck and Marie-Pierre Bousquet and Emmanuelle Mouton-Barbosa and Sarah Cianférani and Odile Burlet-Schiltz and Raphael Guerois and Gilles Labesse and Pierre Tufféry}, year = {2020}, date = {2020-01-01}, journal = {Journal of proteome research}, volume = {19}, number = {7}, pages = {2807--2820}, address = {United States}, abstract = {Protein-protein interactions play a major role in the molecular machinery of life, and various techniques such as AP-MS are dedicated to their identification. However, those techniques return lists of proteins devoid of organizational structure, not detailing which proteins interact with which others. Proposing a hierarchical view of the interactions between the members of the flat list becomes highly tedious for large data sets when done by hand. To help hierarchize this data, we introduce a new bioinformatics protocol that integrates information of the multimeric protein 3D structures available in the Protein Data Bank using remote homology detection, as well as information related to Short Linear Motifs and interaction data from the BioGRID. We illustrate on two unrelated use-cases of different complexity how our approach can be useful to decipher the network of interactions hidden in the list of input proteins, and how it provides added value compared to state-of-the-art resources such as Interactome3D or STRING. Particularly, we show the added value of using homology detection to distinguish between orthologs and paralogs, and to distinguish between core obligate and more facultative interactions. We also demonstrate the potential of considering interactions occurring through Short Linear Motifs.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Protein-protein interactions play a major role in the molecular machinery of life, and various techniques such as AP-MS are dedicated to their identification. However, those techniques return lists of proteins devoid of organizational structure, not detailing which proteins interact with which others. Proposing a hierarchical view of the interactions between the members of the flat list becomes highly tedious for large data sets when done by hand. To help hierarchize this data, we introduce a new bioinformatics protocol that integrates information of the multimeric protein 3D structures available in the Protein Data Bank using remote homology detection, as well as information related to Short Linear Motifs and interaction data from the BioGRID. We illustrate on two unrelated use-cases of different complexity how our approach can be useful to decipher the network of interactions hidden in the list of input proteins, and how it provides added value compared to state-of-the-art resources such as Interactome3D or STRING. Particularly, we show the added value of using homology detection to distinguish between orthologs and paralogs, and to distinguish between core obligate and more facultative interactions. We also demonstrate the potential of considering interactions occurring through Short Linear Motifs. |
Dia, Maya; Gomez, Ludovic; Thibault, Helene; Tessier, Nolwenn; Leon, Christelle; Chouabe, Christophe; Ducreux, Sylvie; Gallo-Bona, Noelle; Tubbs, Emily; Bendridi, Nadia; Chanon, Stephanie; Leray, Aymeric; Belmudes, Lucid; Couté, Yohann; Kurdi, Mazen; Ovize, Michel; Rieusset, Jennifer; Paillard, Melanie Reduced reticulum–mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy Article de journal Basic Research in Cardiology, 115 (6), p. 74, 2020, ISSN: 0300-8428, 1435-1803. @article{dia_reduced_2020, title = {Reduced reticulum–mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy}, author = {Maya Dia and Ludovic Gomez and Helene Thibault and Nolwenn Tessier and Christelle Leon and Christophe Chouabe and Sylvie Ducreux and Noelle Gallo-Bona and Emily Tubbs and Nadia Bendridi and Stephanie Chanon and Aymeric Leray and Lucid Belmudes and Yohann Couté and Mazen Kurdi and Michel Ovize and Jennifer Rieusset and Melanie Paillard}, url = {http://link.springer.com/10.1007/s00395-020-00835-7}, doi = {10.1007/s00395-020-00835-7}, issn = {0300-8428, 1435-1803}, year = {2020}, date = {2020-01-01}, journal = {Basic Research in Cardiology}, volume = {115}, number = {6}, pages = {74}, abstract = {Abstract Type 2 diabetic cardiomyopathy features Ca 2+ signaling abnormalities, notably an altered mitochondrial Ca 2+ handling. We here aimed to study if it might be due to a dysregulation of either the whole Ca 2+ homeostasis, the reticulum–mitochondrial Ca 2+ coupling, and/or the mitochondrial Ca 2+ entry through the uniporter. Following a 16-week high-fat high-sucrose diet (HFHSD), mice developed cardiac insulin resistance, fibrosis, hypertrophy, lipid accumulation, and diastolic dysfunction when compared to standard diet. Ultrastructural and proteomic analyses of cardiac reticulum–mitochondria interface revealed tighter interactions not compatible with Ca 2+ transport in HFHSD cardiomyocytes. Intramyocardial adenoviral injections of Ca 2+ sensors were performed to measure Ca 2+ fluxes in freshly isolated adult cardiomyocytes and to analyze the direct effects of in vivo type 2 diabetes on cardiomyocyte function. HFHSD resulted in a decreased IP3R–VDAC interaction and a reduced IP3-stimulated Ca 2+ transfer to mitochondria, with no changes in reticular Ca 2+ level, cytosolic Ca 2+ transients, and mitochondrial Ca 2+ uniporter function. Disruption of organelle Ca 2+ exchange was associated with decreased mitochondrial bioenergetics and reduced cell contraction, which was rescued by an adenovirus-mediated expression of a reticulum-mitochondria linker. An 8-week diet reversal was able to restore cardiac insulin signaling, Ca 2+ transfer, and cardiac function in HFHSD mice. Therefore, our study demonstrates that the reticulum–mitochondria Ca 2+ miscoupling may play an early and reversible role in the development of diabetic cardiomyopathy by disrupting primarily the mitochondrial bioenergetics. A diet reversal, by counteracting the MAM-induced mitochondrial Ca 2+ dysfunction, might contribute to restore normal cardiac function and prevent the exacerbation of diabetic cardiomyopathy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Type 2 diabetic cardiomyopathy features Ca 2+ signaling abnormalities, notably an altered mitochondrial Ca 2+ handling. We here aimed to study if it might be due to a dysregulation of either the whole Ca 2+ homeostasis, the reticulum–mitochondrial Ca 2+ coupling, and/or the mitochondrial Ca 2+ entry through the uniporter. Following a 16-week high-fat high-sucrose diet (HFHSD), mice developed cardiac insulin resistance, fibrosis, hypertrophy, lipid accumulation, and diastolic dysfunction when compared to standard diet. Ultrastructural and proteomic analyses of cardiac reticulum–mitochondria interface revealed tighter interactions not compatible with Ca 2+ transport in HFHSD cardiomyocytes. Intramyocardial adenoviral injections of Ca 2+ sensors were performed to measure Ca 2+ fluxes in freshly isolated adult cardiomyocytes and to analyze the direct effects of in vivo type 2 diabetes on cardiomyocyte function. HFHSD resulted in a decreased IP3R–VDAC interaction and a reduced IP3-stimulated Ca 2+ transfer to mitochondria, with no changes in reticular Ca 2+ level, cytosolic Ca 2+ transients, and mitochondrial Ca 2+ uniporter function. Disruption of organelle Ca 2+ exchange was associated with decreased mitochondrial bioenergetics and reduced cell contraction, which was rescued by an adenovirus-mediated expression of a reticulum-mitochondria linker. An 8-week diet reversal was able to restore cardiac insulin signaling, Ca 2+ transfer, and cardiac function in HFHSD mice. Therefore, our study demonstrates that the reticulum–mitochondria Ca 2+ miscoupling may play an early and reversible role in the development of diabetic cardiomyopathy by disrupting primarily the mitochondrial bioenergetics. A diet reversal, by counteracting the MAM-induced mitochondrial Ca 2+ dysfunction, might contribute to restore normal cardiac function and prevent the exacerbation of diabetic cardiomyopathy. |
Began, Jakub; Cordier, Baptiste; Březinová, Jana; Delisle, Jordan; Hexnerová, Rozálie; Srb, Pavel; Rampírová, Petra; ž, Milan Ko; Baudet, Mathieu; Couté, Yohann; Galinier, Anne; Veverka, Václav; Doan, Thierry; Strisovsky, Kvido Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH textlessspan style= Article de journal The EMBO Journal, 2020, ISSN: 0261-4189, 1460-2075. @article{began_rhomboid_2020, title = {Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH textlessspan style=}, author = {Jakub Began and Baptiste Cordier and Jana Březinová and Jordan Delisle and Rozálie Hexnerová and Pavel Srb and Petra Rampírová and Milan Ko{ž}íšek and Mathieu Baudet and Yohann Couté and Anne Galinier and Václav Veverka and Thierry Doan and Kvido Strisovsky}, url = {https://onlinelibrary.wiley.com/doi/abs/10.15252/embj.2019102935}, doi = {10.15252/embj.2019102935}, issn = {0261-4189, 1460-2075}, year = {2020}, date = {2020-01-01}, journal = {The EMBO Journal}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Lezzerini, Marco; Penzo, Marianna; ç, Marie-Fran; Marques Dos Santos Vieira, Carolina ; Saby, Manon; Elfrink, Hyung L; Diets, Illja J; Hesse, Anne-Marie; Couté, Yohann; Gastou, Marc; Nin-Velez, Alexandra; Nikkels, Peter G J; Olson, Alexandra N; Zonneveld-Huijssoon, Evelien; Jongmans, Marjolijn C J; Zhang, GuangJun; van Weeghel, Michel; Houtkooper, Riekelt H; Wlodarski, Marcin W; Kuiper, Roland P; Bierings, Marc B; van der Werff Ten Bosch, Jutte ; Leblanc, Thierry; Montanaro, Lorenzo; Dinman, Jonathan D; Da Costa, Lydie ; Gleizes, Pierre-Emmanuel; MacInnes, Alyson W Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism Article de journal Nucleic Acids Research, 48 (2), p. 770–787, 2020, ISSN: 1362-4962. @article{lezzerini_ribosomal_2020, title = {Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism}, author = {Marco Lezzerini and Marianna Penzo and Marie-Fran{ç}oise O'Donohue and Carolina {Marques Dos Santos Vieira} and Manon Saby and Hyung L Elfrink and Illja J Diets and Anne-Marie Hesse and Yohann Couté and Marc Gastou and Alexandra Nin-Velez and Peter G J Nikkels and Alexandra N Olson and Evelien Zonneveld-Huijssoon and Marjolijn C J Jongmans and GuangJun Zhang and Michel van Weeghel and Riekelt H Houtkooper and Marcin W Wlodarski and Roland P Kuiper and Marc B Bierings and Jutte {van der Werff Ten Bosch} and Thierry Leblanc and Lorenzo Montanaro and Jonathan D Dinman and Lydie {Da Costa} and Pierre-Emmanuel Gleizes and Alyson W MacInnes}, doi = {10.1093/nar/gkz1042}, issn = {1362-4962}, year = {2020}, date = {2020-01-01}, journal = {Nucleic Acids Research}, volume = {48}, number = {2}, pages = {770--787}, abstract = {Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5'UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80S monosome reduction, the downstream effects are remarkably different. Cells carrying the 5'UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5'UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5'UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80S monosome reduction, the downstream effects are remarkably different. Cells carrying the 5'UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5'UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts. |
Crespo, Marion; Luense, Lacey J; Arlotto, Marie; Jialei, Hu; Dorsey, Jean; Garcia-Oliver, Encar; Shah, Parisha P; Pflieger, Delphine; Berger, Shelley L; ô, Jér Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark Article de journal Epigenetics & Chromatin, 13 (35), p. 1–23, 2020. @article{crespo_systematic_2020, title = {Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark}, author = {Marion Crespo and Lacey J Luense and Marie Arlotto and Hu Jialei and Jean Dorsey and Encar Garcia-Oliver and Parisha P Shah and Delphine Pflieger and Shelley L Berger and Jér{ô}me Govin}, url = {https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-020-00349-5#citeas}, doi = {10.1186/s13072-020-00349-5}, year = {2020}, date = {2020-01-01}, journal = {Epigenetics & Chromatin}, volume = {13}, number = {35}, pages = {1--23}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Hahn, Friedrich; Niesar, Aischa; Wangen, Christina; Wild, Markus; Grau, Benedikt; Herrmann, Lars; Capci, Aysun; Adrait, Annie; Couté, Yohann; Tsogoeva, Svetlana B; Marschall, Manfred Target verification of artesunate-related antiviral drugs: assessing the role of mitochondrial and regulatory proteins by click chemistry and fluorescence labeling Article de journal Antiviral Research, p. 104861, 2020, ISSN: 01663542. @article{hahn_target_2020, title = {Target verification of artesunate-related antiviral drugs: assessing the role of mitochondrial and regulatory proteins by click chemistry and fluorescence labeling}, author = {Friedrich Hahn and Aischa Niesar and Christina Wangen and Markus Wild and Benedikt Grau and Lars Herrmann and Aysun Capci and Annie Adrait and Yohann Couté and Svetlana B Tsogoeva and Manfred Marschall}, url = {https://linkinghub.elsevier.com/retrieve/pii/S0166354220302758}, doi = {10.1016/j.antiviral.2020.104861}, issn = {01663542}, year = {2020}, date = {2020-01-01}, journal = {Antiviral Research}, pages = {104861}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Vandenbrouck, Yves; Pineau, Charles; Lane, Lydie The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology Article de journal Journal of Proteome Research, 2020, ISSN: 1535-3907. @article{vandenbrouck_functionally_2020, title = {The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology}, author = {Yves Vandenbrouck and Charles Pineau and Lydie Lane}, doi = {10.1021/acs.jproteome.0c00516}, issn = {1535-3907}, year = {2020}, date = {2020-01-01}, journal = {Journal of Proteome Research}, abstract = {In the context of the Human Proteome Project, we built an inventory of 412 functionally unannotated human proteins for which experimental evidence at the protein level exists (uPE1) and which are highly expressed in tissues involved in human male reproduction. We implemented a strategy combining literature mining, bioinformatics tools to collate annotation and experimental information from specific molecular public resources, and efficient visualization tools to put these unknown proteins into their biological context (protein complexes, tissue and subcellular location, expression pattern). The gathered knowledge allowed pinpointing five uPE1 for which a function has recently been proposed and which should be updated in protein knowledge bases. Furthermore, this bioinformatics strategy allowed to build new functional hypotheses for five other uPE1s in link with phenotypic traits that are specific to male reproductive function such as ciliogenesis/flagellum formation in germ cells (CCDC112 and TEX9), chromatin remodeling (C3orf62) and spermatozoon maturation (CCDC183). We also discussed the enigmatic case of MAGEB proteins, a poorly documented cancer/testis antigen subtype. Tools used and computational outputs produced during this study are freely accessible via ProteoRE (http://www.proteore.org), a Galaxy-based instance, for reuse purposes. We propose these five uPE1s should be investigated in priority by expert laboratories and hope that this inventory and shared resources will stimulate the interest of the community of reproductive biology.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In the context of the Human Proteome Project, we built an inventory of 412 functionally unannotated human proteins for which experimental evidence at the protein level exists (uPE1) and which are highly expressed in tissues involved in human male reproduction. We implemented a strategy combining literature mining, bioinformatics tools to collate annotation and experimental information from specific molecular public resources, and efficient visualization tools to put these unknown proteins into their biological context (protein complexes, tissue and subcellular location, expression pattern). The gathered knowledge allowed pinpointing five uPE1 for which a function has recently been proposed and which should be updated in protein knowledge bases. Furthermore, this bioinformatics strategy allowed to build new functional hypotheses for five other uPE1s in link with phenotypic traits that are specific to male reproductive function such as ciliogenesis/flagellum formation in germ cells (CCDC112 and TEX9), chromatin remodeling (C3orf62) and spermatozoon maturation (CCDC183). We also discussed the enigmatic case of MAGEB proteins, a poorly documented cancer/testis antigen subtype. Tools used and computational outputs produced during this study are freely accessible via ProteoRE (http://www.proteore.org), a Galaxy-based instance, for reuse purposes. We propose these five uPE1s should be investigated in priority by expert laboratories and hope that this inventory and shared resources will stimulate the interest of the community of reproductive biology. |
Ngo, Tuan-Dung; Perdu, Caroline; Jneid, Bakhos; Ragno, Michel; Novion Ducassou, Julia ; Kraut, Alexandra; Couté, Yohann; Stopford, Charles; Attree, Ina; Rietsch, Arne; Faudry, Eric The PopN gate-keeper complex acts on the ATPase PscN to regulate the T3SS secretion switch from early to middle substrates in Pseudomonas aeruginosa Article de journal Journal of Molecular Biology, 2020, ISSN: 0022-2836. @article{ngo_popn_2020, title = {The PopN gate-keeper complex acts on the ATPase PscN to regulate the T3SS secretion switch from early to middle substrates in Pseudomonas aeruginosa}, author = {Tuan-Dung Ngo and Caroline Perdu and Bakhos Jneid and Michel Ragno and Julia {Novion Ducassou} and Alexandra Kraut and Yohann Couté and Charles Stopford and Ina Attree and Arne Rietsch and Eric Faudry}, url = {http://www.sciencedirect.com/science/article/pii/S0022283620306008}, doi = {10.1016/j.jmb.2020.10.024}, issn = {0022-2836}, year = {2020}, date = {2020-01-01}, journal = {Journal of Molecular Biology}, abstract = {Pseudomonas aeruginosa is an opportunistic bacterium of which the main virulence factor is the Type III Secretion System. The ATPase of this machinery, PscN (SctN), is thought to be localized at the base of the secretion apparatus and to participate in the recognition, chaperone dissociation and unfolding of exported T3SS proteins. In this work, a protein-protein interaction ELISA revealed the interaction of PscN with a wide range of exported T3SS proteins including the needle, translocator, gate-keeper and effector. These interactions were further confirmed by Microscale Thermophoresis that also indicated a preferential interaction of PscN with secreted proteins or protein-chaperone complex rather than with chaperones alone, in line with the release of the chaperones in the bacterial cytoplasm after the dissociation from their exported proteins. Moreover, we suggest a new role of the gate-keeper complex and the ATPase in the regulation of early substrates recognition by the T3SS. This finding sheds a new light on the mechanism of secretion switching from early to middle substrates in P. aeruginosa.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Pseudomonas aeruginosa is an opportunistic bacterium of which the main virulence factor is the Type III Secretion System. The ATPase of this machinery, PscN (SctN), is thought to be localized at the base of the secretion apparatus and to participate in the recognition, chaperone dissociation and unfolding of exported T3SS proteins. In this work, a protein-protein interaction ELISA revealed the interaction of PscN with a wide range of exported T3SS proteins including the needle, translocator, gate-keeper and effector. These interactions were further confirmed by Microscale Thermophoresis that also indicated a preferential interaction of PscN with secreted proteins or protein-chaperone complex rather than with chaperones alone, in line with the release of the chaperones in the bacterial cytoplasm after the dissociation from their exported proteins. Moreover, we suggest a new role of the gate-keeper complex and the ATPase in the regulation of early substrates recognition by the T3SS. This finding sheds a new light on the mechanism of secretion switching from early to middle substrates in P. aeruginosa. |
Lamboux, Aline; Couchonnal-Bedoya, Eduardo; Guillaud, Olivier; Laurencin, Chloé; ç, Laurence Lion-Fran; Belmalih, Abdelouahed; Mintz, Elisabeth; Brun, Virginie; Bost, Muriel; Lachaux, Alain; Balter, Vincent The blood copper isotopic composition is a prognostic indicator of the hepatic injury in Wilson disease Article de journal Metallomics: Integrated Biometal Science, 2020, ISSN: 1756-591X. @article{lamboux_blood_2020, title = {The blood copper isotopic composition is a prognostic indicator of the hepatic injury in Wilson disease}, author = {Aline Lamboux and Eduardo Couchonnal-Bedoya and Olivier Guillaud and Chloé Laurencin and Laurence Lion-Fran{ç}ois and Abdelouahed Belmalih and Elisabeth Mintz and Virginie Brun and Muriel Bost and Alain Lachaux and Vincent Balter}, doi = {10.1039/d0mt00167h}, issn = {1756-591X}, year = {2020}, date = {2020-01-01}, journal = {Metallomics: Integrated Biometal Science}, abstract = {Wilson disease (WD) is an autosomal recessive disorder of copper (Cu) metabolism. The gene responsible for WD, ATP7B, is involved in the cellular transport of Cu, and mutations in the ATP7B gene induce accumulation of Cu in the liver and ultimately in the brain. In a pilot study, the natural variations of copper stable isotope ratios (65Cu/63Cu) in the serum of WD patients have been shown to differ from that of healthy controls. In the present study, we challenged these first results by measuring the 65Cu/63Cu ratios in the blood of treated (n = 25), naïve patients (n = 11) and age matched healthy controls (n = 75). The results show that naïve patients and healthy controls exhibit undistinguishable 65Cu/63Cu ratios, implying that the Cu isotopic ratio cannot serve as a reliable diagnostic biomarker. The type of treatment (d-penicillamine vs. triethylenetetramine) does not affect the 65Cu/63Cu ratios in WD patients, which remain constant regardless of the type and duration of the treatment. In addition, the 65Cu/63Cu ratios do not vary in naïve patients after the onset of the treatment. However, the 65Cu/63Cu ratios decrease with the degree of liver fibrosis and the gradient of the phenotypic presentation, i.e. presymptomatic, hepatic and neurologic. To get insights into the mechanisms at work, we study the effects of the progress of the WD on the organism by measuring the Cu concentrations and the 65Cu/63Cu ratios in the liver, feces and plasma of 12 and 45 week old Atp7b-/- mice. The evolution of the 65Cu/63Cu ratios is marked by a decrease in all tissues. The results show that 63Cu accumulates in the liver preferentially to 65Cu due to the preferential cellular entry of 63Cu and the impairment of the 63Cu exit by ceruloplasmin. The hepatic accumulation of monovalent 63Cu+ is likely to fuel the production of free radicals, which is potentially an explanation of the pathogenicity of WD. Altogether, the results suggest that the blood 65Cu/63Cu ratio recapitulates WD progression and is a potential prognostic biomarker of WD.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Wilson disease (WD) is an autosomal recessive disorder of copper (Cu) metabolism. The gene responsible for WD, ATP7B, is involved in the cellular transport of Cu, and mutations in the ATP7B gene induce accumulation of Cu in the liver and ultimately in the brain. In a pilot study, the natural variations of copper stable isotope ratios (65Cu/63Cu) in the serum of WD patients have been shown to differ from that of healthy controls. In the present study, we challenged these first results by measuring the 65Cu/63Cu ratios in the blood of treated (n = 25), naïve patients (n = 11) and age matched healthy controls (n = 75). The results show that naïve patients and healthy controls exhibit undistinguishable 65Cu/63Cu ratios, implying that the Cu isotopic ratio cannot serve as a reliable diagnostic biomarker. The type of treatment (d-penicillamine vs. triethylenetetramine) does not affect the 65Cu/63Cu ratios in WD patients, which remain constant regardless of the type and duration of the treatment. In addition, the 65Cu/63Cu ratios do not vary in naïve patients after the onset of the treatment. However, the 65Cu/63Cu ratios decrease with the degree of liver fibrosis and the gradient of the phenotypic presentation, i.e. presymptomatic, hepatic and neurologic. To get insights into the mechanisms at work, we study the effects of the progress of the WD on the organism by measuring the Cu concentrations and the 65Cu/63Cu ratios in the liver, feces and plasma of 12 and 45 week old Atp7b-/- mice. The evolution of the 65Cu/63Cu ratios is marked by a decrease in all tissues. The results show that 63Cu accumulates in the liver preferentially to 65Cu due to the preferential cellular entry of 63Cu and the impairment of the 63Cu exit by ceruloplasmin. The hepatic accumulation of monovalent 63Cu+ is likely to fuel the production of free radicals, which is potentially an explanation of the pathogenicity of WD. Altogether, the results suggest that the blood 65Cu/63Cu ratio recapitulates WD progression and is a potential prognostic biomarker of WD. |
Roblin, Clarisse; Chiumento, Steve; Bornet, Olivier; Nouailler, Matthieu; Müller, Christina S; Jeannot, Katy; Basset, Christian; Kieffer-Jaquinod, Sylvie; Couté, Yohann; Torelli, Stéphane; Le Pape, Laurent ; Schünemann, Volker; Olleik, Hamza; De La Villeon, Bruno ; Sockeel, Philippe; Di Pasquale, Eric ; Nicoletti, Cendrine; Vidal, Nicolas; Poljak, Leonora; Iranzo, Olga; Giardina, Thierry; Fons, Michel; Devillard, Estelle; Polard, Patrice; Maresca, Marc; Perrier, Josette; Atta, Mohamed; ç, Fran; Lafond, Mickael; Duarte, Victor The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties Article de journal Proceedings of the National Academy of Sciences of the United States of America, 2020, ISSN: 1091-6490. @article{roblin_unusual_2020, title = {The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties}, author = {Clarisse Roblin and Steve Chiumento and Olivier Bornet and Matthieu Nouailler and Christina S Müller and Katy Jeannot and Christian Basset and Sylvie Kieffer-Jaquinod and Yohann Couté and Stéphane Torelli and Laurent {Le Pape} and Volker Schünemann and Hamza Olleik and Bruno {De La Villeon} and Philippe Sockeel and Eric {Di Pasquale} and Cendrine Nicoletti and Nicolas Vidal and Leonora Poljak and Olga Iranzo and Thierry Giardina and Michel Fons and Estelle Devillard and Patrice Polard and Marc Maresca and Josette Perrier and Mohamed Atta and Fran{ç}oise Guerlesquin and Mickael Lafond and Victor Duarte}, doi = {10.1073/pnas.2004045117}, issn = {1091-6490}, year = {2020}, date = {2020-01-01}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, abstract = {The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues. |
Sokolovska, Nataliya; Permiakova, Olga; Forslund, Sofia K; Zucker, Jean-Daniel Using Unlabeled Data to Discover Bivariate Causality with Deep Restricted Boltzmann Machines Article de journal IEEE/ACM transactions on computational biology and bioinformatics, 17 (1), p. 358–364, 2020, ISSN: 1557-9964. @article{sokolovska_using_2020, title = {Using Unlabeled Data to Discover Bivariate Causality with Deep Restricted Boltzmann Machines}, author = {Nataliya Sokolovska and Olga Permiakova and Sofia K Forslund and Jean-Daniel Zucker}, doi = {10.1109/TCBB.2018.2879504}, issn = {1557-9964}, year = {2020}, date = {2020-01-01}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {17}, number = {1}, pages = {358--364}, abstract = {An important question in microbiology is whether treatment causes changes in gut flora, and whether it also affects metabolism. The reconstruction of causal relations purely from non-temporal observational data is challenging. We address the problem of causal inference in a bivariate case, where the joint distribution of two variables is observed. We consider, in particular, data on discrete domains. The state-of-the-art causal inference methods for continuous data suffer from high computational complexity. Some modern approaches are not suitable for categorical data, and others need to estimate and fix multiple hyper-parameters. In this contribution, we introduce a novel method of causal inference which is based on the widely used assumption that if X causes Y, then P(X) and P(Y$backslash$textbarX) are independent. We propose to explore a semi-supervised approach where P(Y$backslash$textbarX) and P(X) are estimated from labeled and unlabeled data respectively, whereas the marginal probability is estimated potentially from much more (cheap unlabeled) data than the conditional distribution. We validate the proposed method on the standard cause-effect pairs. We illustrate by experiments on several benchmarks of biological network reconstruction that the proposed approach is very competitive in terms of computational time and accuracy compared to the state-of-the-art methods. Finally, we apply the proposed method to an original medical task where we study whether drugs confound human metagenome.}, keywords = {}, pubstate = {published}, tppubtype = {article} } An important question in microbiology is whether treatment causes changes in gut flora, and whether it also affects metabolism. The reconstruction of causal relations purely from non-temporal observational data is challenging. We address the problem of causal inference in a bivariate case, where the joint distribution of two variables is observed. We consider, in particular, data on discrete domains. The state-of-the-art causal inference methods for continuous data suffer from high computational complexity. Some modern approaches are not suitable for categorical data, and others need to estimate and fix multiple hyper-parameters. In this contribution, we introduce a novel method of causal inference which is based on the widely used assumption that if X causes Y, then P(X) and P(Y$backslash$textbarX) are independent. We propose to explore a semi-supervised approach where P(Y$backslash$textbarX) and P(X) are estimated from labeled and unlabeled data respectively, whereas the marginal probability is estimated potentially from much more (cheap unlabeled) data than the conditional distribution. We validate the proposed method on the standard cause-effect pairs. We illustrate by experiments on several benchmarks of biological network reconstruction that the proposed approach is very competitive in terms of computational time and accuracy compared to the state-of-the-art methods. Finally, we apply the proposed method to an original medical task where we study whether drugs confound human metagenome. |
Allison, T M; Barran, P E; Benesch, J L P; Cianferani, S; Degiacomi, M T; Gabelica, V; Grandori, R; Marklund, E G; Menneteau, T; Migas, L G; Politis, A; Sharon, M; Sobott, F; Thalassinos, K Software requirements for the analysis and interpretation of native ion mobility mass spectrometry data Article de journal Anal Chem, 2020, ISSN: 1520-6882 (Electronic) 0003-2700 (Linking), (review, pas de projet LSMBO). @article{674, title = {Software requirements for the analysis and interpretation of native ion mobility mass spectrometry data}, author = {T M Allison and P E Barran and J L P Benesch and S Cianferani and M T Degiacomi and V Gabelica and R Grandori and E G Marklund and T Menneteau and L G Migas and A Politis and M Sharon and F Sobott and K Thalassinos}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32649184}, doi = {10.1021/acs.analchem.9b05792}, issn = {1520-6882 (Electronic) 0003-2700 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Anal Chem}, note = {review, pas de projet LSMBO}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Allison, T M; Barran, P E; Cianferani, S; Degiacomi, M T; Gabelica, V; Grandori, R; Marklund, E G; Menneteau, T; Migas, L G; Politis, A; Sharon, M; Sobott, F; Thalassinos, K; Benesch, J L P Computational strategies and challenges for using native ion mobility mass spectrometry in biophysics and structural biology Article de journal Anal Chem, 2020, ISSN: 1520-6882 (Electronic) 0003-2700 (Linking), (review pas de projet LSMBO). @article{673b, title = {Computational strategies and challenges for using native ion mobility mass spectrometry in biophysics and structural biology}, author = {T M Allison and P E Barran and S Cianferani and M T Degiacomi and V Gabelica and R Grandori and E G Marklund and T Menneteau and L G Migas and A Politis and M Sharon and F Sobott and K Thalassinos and J L P Benesch}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32667808}, doi = {10.1021/acs.analchem.9b05791}, issn = {1520-6882 (Electronic) 0003-2700 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Anal Chem}, note = {review pas de projet LSMBO}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Botzanowski, T; Hernandez-Alba, O; Malissard, M; Wagner-Rousset, E; Desligniere, E; Colas, O; Haeuw, J F; Beck, A; Cianferani, S Middle Level IM-MS and CIU Experiments for Improved Therapeutic Immunoglobulin Subclass Fingerprinting Article de journal Anal Chem, 92 (13), p. 8827-8835, 2020, ISSN: 1520-6882 (Electronic) 0003-2700 (Linking). @article{663b, title = {Middle Level IM-MS and CIU Experiments for Improved Therapeutic Immunoglobulin Subclass Fingerprinting}, author = {T Botzanowski and O Hernandez-Alba and M Malissard and E Wagner-Rousset and E Desligniere and O Colas and J F Haeuw and A Beck and S Cianferani}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32453570}, doi = {10.1021/acs.analchem.0c00293}, issn = {1520-6882 (Electronic) 0003-2700 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Anal Chem}, volume = {92}, number = {13}, pages = {8827-8835}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Castro, C N; Rosenzwajg, M; Carapito, R; Shahrooei, M; Konantz, M; Khan, A; Miao, Z; Gross, M; Tranchant, T; Radosavljevic, M; Paul, N; Stemmelen, T; Pitoiset, F; Hirschler, A; Nespola, B; Molitor, A; Rolli, V; Pichot, A; Faletti, L E; Rinaldi, B; Friant, S; Mednikov, M; Karauzum, H; Aman, M J; Carapito, C; Lengerke, C; Ziaee, V; Eyaid, W; Ehl, S; Alroqi, F; Parvaneh, N; Bahram, S NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation Article de journal J Exp Med, 217 (12), 2020, ISSN: 1540-9538 (Electronic) 0022-1007 (Linking), (????). @article{679b, title = {NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation}, author = {C N Castro and M Rosenzwajg and R Carapito and M Shahrooei and M Konantz and A Khan and Z Miao and M Gross and T Tranchant and M Radosavljevic and N Paul and T Stemmelen and F Pitoiset and A Hirschler and B Nespola and A Molitor and V Rolli and A Pichot and L E Faletti and B Rinaldi and S Friant and M Mednikov and H Karauzum and M J Aman and C Carapito and C Lengerke and V Ziaee and W Eyaid and S Ehl and F Alroqi and N Parvaneh and S Bahram}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32766723}, doi = {10.1084/jem.20192275}, issn = {1540-9538 (Electronic) 0022-1007 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {J Exp Med}, volume = {217}, number = {12}, note = {????}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Chabrol, E; Stojko, J; Nicolas, A; Botzanowski, T; Fould, B; Antoine, M; Cianferani, S; Ferry, G; Boutin, J A VHH characterization.Recombinant VHHs: Production, characterization and affinity Article de journal Anal Biochem, 589 , p. 113491, 2020, ISSN: 1096-0309 (Electronic) 0003-2697 (Linking). @article{659, title = {VHH characterization.Recombinant VHHs: Production, characterization and affinity}, author = {E Chabrol and J Stojko and A Nicolas and T Botzanowski and B Fould and M Antoine and S Cianferani and G Ferry and J A Boutin}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31676284}, doi = {10.1016/j.ab.2019.113491}, issn = {1096-0309 (Electronic) 0003-2697 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Anal Biochem}, volume = {589}, pages = {113491}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Charles, L; Mondal, T; Greff, V; Razzini, M; Monnier, V; Burel, A; Carapito, C; Lutz, J F Optimal conditions for tandem mass spectrometric sequencing of information-containing nitrogen-substituted polyurethanes Article de journal Rapid Commun Mass Spectrom, 34 (14), p. e8815, 2020, ISSN: 1097-0231 (Electronic) 0951-4198 (Linking), (????). @article{678, title = {Optimal conditions for tandem mass spectrometric sequencing of information-containing nitrogen-substituted polyurethanes}, author = {L Charles and T Mondal and V Greff and M Razzini and V Monnier and A Burel and C Carapito and J F Lutz}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32311797}, doi = {10.1002/rcm.8815}, issn = {1097-0231 (Electronic) 0951-4198 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Rapid Commun Mass Spectrom}, volume = {34}, number = {14}, pages = {e8815}, note = {????}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Ciudad, S; Puig, E; Botzanowski, T; Meigooni, M; Arango, A S; Do, J; Mayzel, M; Bayoumi, M; Chaignepain, S; Maglia, G; Cianferani, S; Orekhov, V; Tajkhorshid, E; Bardiaux, B; Carulla, N Abeta(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage Article de journal Nat Commun, 11 (1), p. 3014, 2020, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking), (2018/12). @article{666, title = {Abeta(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage}, author = {S Ciudad and E Puig and T Botzanowski and M Meigooni and A S Arango and J Do and M Mayzel and M Bayoumi and S Chaignepain and G Maglia and S Cianferani and V Orekhov and E Tajkhorshid and B Bardiaux and N Carulla}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32541820}, doi = {10.1038/s41467-020-16566-1}, issn = {2041-1723 (Electronic) 2041-1723 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Nat Commun}, volume = {11}, number = {1}, pages = {3014}, note = {2018/12}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Dovgan, I; Ehkirch, A; Lehot, V; Kuhn, I; Koniev, O; Kolodych, S; Hentz, A; Ripoll, M; Ursuegui, S; Nothisen, M; Cianferani, S; Wagner, A On the use of DNA as a linker in antibody-drug conjugates: synthesis, stability and in vitro potency Article de journal Sci Rep, 10 (1), p. 7691, 2020, ISSN: 2045-2322 (Electronic) 2045-2322 (Linking), (2019-05). @article{667, title = {On the use of DNA as a linker in antibody-drug conjugates: synthesis, stability and in vitro potency}, author = {I Dovgan and A Ehkirch and V Lehot and I Kuhn and O Koniev and S Kolodych and A Hentz and M Ripoll and S Ursuegui and M Nothisen and S Cianferani and A Wagner}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32376903}, doi = {10.1038/s41598-020-64518-y}, issn = {2045-2322 (Electronic) 2045-2322 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Sci Rep}, volume = {10}, number = {1}, pages = {7691}, note = {2019-05}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Duivelshof, B L; Desligniere, E; Hernandez-Alba, O; Ehkirch, A; Toftevall, H; Sjogren, J; Cianferani, S; Beck, A; Guillarme, D; D'Atri, V Anal Chem, 92 (12), p. 8170-8177, 2020, ISSN: 1520-6882 (Electronic) 0003-2700 (Linking), (pas de manips au LSMBO). @article{668b, title = {Glycan-Mediated Technology for Obtaining Homogeneous Site-Specific Conjugated Antibody-Drug Conjugates: Synthesis and Analytical Characterization by Using Complementary Middle-up LC/HRMS Analysis}, author = {B L Duivelshof and E Desligniere and O Hernandez-Alba and A Ehkirch and H Toftevall and J Sjogren and S Cianferani and A Beck and D Guillarme and V D'Atri}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32407621}, doi = {10.1021/acs.analchem.0c00282}, issn = {1520-6882 (Electronic) 0003-2700 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Anal Chem}, volume = {92}, number = {12}, pages = {8170-8177}, note = {pas de manips au LSMBO}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Farras, M; Miret, J; Camps, M; Roman, R; Martinez, O; Pujol, X; Erb, S; Ehkirch, A; Cianferani, S; Casablancas, A; Cairo, J J Homogeneous antibody-drug conjugates: DAR 2 anti-HER2 obtained by conjugation on isolated light chain followed by mAb assembly Article de journal MAbs, 12 (1), p. 1702262, 2020, ISSN: 1942-0870 (Electronic) 1942-0862 (Linking), (2018/06). @article{655, title = {Homogeneous antibody-drug conjugates: DAR 2 anti-HER2 obtained by conjugation on isolated light chain followed by mAb assembly}, author = {M Farras and J Miret and M Camps and R Roman and O Martinez and X Pujol and S Erb and A Ehkirch and S Cianferani and A Casablancas and J J Cairo}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31876436}, doi = {10.1080/19420862.2019.1702262}, issn = {1942-0870 (Electronic) 1942-0862 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {MAbs}, volume = {12}, number = {1}, pages = {1702262}, note = {2018/06}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Hernandez-Alba, O; Ehkirch, A; Beck, A; Cianferani, S Analysis of ADCs by Native Mass Spectrometry Article de journal Methods Mol Biol, 2078 , p. 197-211, 2020, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking), (review). @article{656, title = {Analysis of ADCs by Native Mass Spectrometry}, author = {O Hernandez-Alba and A Ehkirch and A Beck and S Cianferani}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31643058}, doi = {10.1007/978-1-4939-9929-3_13}, issn = {1940-6029 (Electronic) 1064-3745 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Methods Mol Biol}, volume = {2078}, pages = {197-211}, note = {review}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Humbert, N; Kovalenko, L; Saladini, F; Giannini, A; Pires, M; Botzanowski, T; Cherenok, S; Boudier, C; Sharma, K K; Real, E; Zaporozhets, O A; Cianferani, S; Seguin-Devaux, C; Poggialini, F; Botta, M; Zazzi, M; Kalchenko, V I; Mori, M; Mely, Y ACS Infect Dis, 6 (4), p. 687-702, 2020, ISSN: 2373-8227 (Electronic) 2373-8227 (Linking). @article{658, title = {(Thia)calixarenephosphonic Acids as Potent Inhibitors of the Nucleic Acid Chaperone Activity of the HIV-1 Nucleocapsid Protein with a New Binding Mode and Multitarget Antiviral Activity}, author = {N Humbert and L Kovalenko and F Saladini and A Giannini and M Pires and T Botzanowski and S Cherenok and C Boudier and K K Sharma and E Real and O A Zaporozhets and S Cianferani and C Seguin-Devaux and F Poggialini and M Botta and M Zazzi and V I Kalchenko and M Mori and Y Mely}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32045204}, doi = {10.1021/acsinfecdis.9b00290}, issn = {2373-8227 (Electronic) 2373-8227 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {ACS Infect Dis}, volume = {6}, number = {4}, pages = {687-702}, abstract = {The nucleocapsid protein (NC) is a highly conserved protein that plays key roles in HIV-1 replication through its nucleic acid chaperone properties mediated by its two zinc fingers and basic residues. NC is a promising target for antiviral therapy, particularly to control viral strains resistant to currently available drugs. Since calixarenes with antiviral properties have been described, we explored the ability of calixarene hydroxymethylphosphonic or sulfonic acids to inhibit NC chaperone properties and exhibit antiviral activity. By using fluorescence-based assays, we selected four calixarenes inhibiting NC chaperone activity with submicromolar IC50 values. These compounds were further shown by mass spectrometry, isothermal titration calorimetry, and fluorescence anisotropy to bind NC with no zinc ejection and to compete with nucleic acids for the binding to NC. Molecular dynamic simulations further indicated that these compounds interact via their phosphonate or sulfonate groups with the basic surface of NC but not with the hydrophobic plateau at the top of the folded fingers. Cellular studies showed that the most soluble compound CIP201 inhibited the infectivity of wild-type and drug-resistant HIV-1 strains at low micromolar concentrations, primarily targeting the early steps of HIV-1 replication. Moreover, CIP201 was also found to inhibit the flipping and polymerization activity of reverse transcriptase. Calixarenes thus form a class of noncovalent NC inhibitors, endowed with a new binding mode and multitarget antiviral activity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The nucleocapsid protein (NC) is a highly conserved protein that plays key roles in HIV-1 replication through its nucleic acid chaperone properties mediated by its two zinc fingers and basic residues. NC is a promising target for antiviral therapy, particularly to control viral strains resistant to currently available drugs. Since calixarenes with antiviral properties have been described, we explored the ability of calixarene hydroxymethylphosphonic or sulfonic acids to inhibit NC chaperone properties and exhibit antiviral activity. By using fluorescence-based assays, we selected four calixarenes inhibiting NC chaperone activity with submicromolar IC50 values. These compounds were further shown by mass spectrometry, isothermal titration calorimetry, and fluorescence anisotropy to bind NC with no zinc ejection and to compete with nucleic acids for the binding to NC. Molecular dynamic simulations further indicated that these compounds interact via their phosphonate or sulfonate groups with the basic surface of NC but not with the hydrophobic plateau at the top of the folded fingers. Cellular studies showed that the most soluble compound CIP201 inhibited the infectivity of wild-type and drug-resistant HIV-1 strains at low micromolar concentrations, primarily targeting the early steps of HIV-1 replication. Moreover, CIP201 was also found to inhibit the flipping and polymerization activity of reverse transcriptase. Calixarenes thus form a class of noncovalent NC inhibitors, endowed with a new binding mode and multitarget antiviral activity. |
Kenny, H C; Tascher, G; Ziemianin, A; Rudwill, F; Zahariev, A; Chery, I; Gauquelin-Koch, G; Barielle, M P; Heer, M; Blanc, S; O'Gorman, D J; Bertile, F J Proteome Res, 19 (8), p. 3438-3451, 2020, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking), (2011/34). @article{675, title = {Effectiveness of Resistive Vibration Exercise and Whey Protein Supplementation Plus Alkaline Salt on the Skeletal Muscle Proteome Following 21 Days of Bed Rest in Healthy Males}, author = {H C Kenny and G Tascher and A Ziemianin and F Rudwill and A Zahariev and I Chery and G Gauquelin-Koch and M P Barielle and M Heer and S Blanc and D J O'Gorman and F Bertile}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32609523}, doi = {10.1021/acs.jproteome.0c00256}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {J Proteome Res}, volume = {19}, number = {8}, pages = {3438-3451}, note = {2011/34}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Laurens, C; Parmar, A; Murphy, E; Carper, D; Lair, B; Maes, P; Vion, J; Boulet, N; Fontaine, C; Marquès, M; Larrouy, D; Harant, I; Thalamas, C; Montastier, E; Caspar-Baugil, S; Bourlier, V; Tavernier, G; Grolleau, J L; Bouloumié, A; Langin, D; Viguerie, N; Bertile, F; Blanc, S; Glisezinski, De I; O’Gorman, D; Moro, C Growth and differentiation factor 15 is secreted by skeletal muscle during exercise and promotes lipolysis in humans Article de journal JCI Insight, 5 (6), p. E131870, 2020, (2016/26). @article{661, title = {Growth and differentiation factor 15 is secreted by skeletal muscle during exercise and promotes lipolysis in humans}, author = {C Laurens and A Parmar and E Murphy and D Carper and B Lair and P Maes and J Vion and N Boulet and C Fontaine and M Marquès and D Larrouy and I Harant and C Thalamas and E Montastier and S Caspar-Baugil and V Bourlier and G Tavernier and J L Grolleau and A Bouloumié and D Langin and N Viguerie and F Bertile and S Blanc and I De Glisezinski and D O’Gorman and C Moro}, year = {2020}, date = {2020-01-01}, journal = {JCI Insight}, volume = {5}, number = {6}, pages = {E131870}, note = {2016/26}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Lefeuvre, B; Cantero, P; Ehret-Sabatier, L; Lenormand, C; Barthel, C; Po, C; Parveen, N; Grillon, A; Jaulhac, B; Boulanger, N Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials Article de journal Sci Rep, 10 (1), p. 10552, 2020, ISSN: 2045-2322 (Electronic) 2045-2322 (Linking), (2012/30). @article{664b, title = {Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials}, author = {B Lefeuvre and P Cantero and L Ehret-Sabatier and C Lenormand and C Barthel and C Po and N Parveen and A Grillon and B Jaulhac and N Boulanger}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32601348}, doi = {10.1038/s41598-020-67440-5}, issn = {2045-2322 (Electronic) 2045-2322 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Sci Rep}, volume = {10}, number = {1}, pages = {10552}, note = {2012/30}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Luu, B E; Lefai, E; Giroud, S; Swenson, J E; Chazarin, B; Gauquelin-Koch, G; Arnemo, J M; Evans, A L; Bertile, F; Storey, K B MicroRNAs facilitate skeletal muscle maintenance and metabolic suppression in hibernating brown bears Article de journal J Cell Physiol, 235 (4), p. 3984-3993, 2020, ISSN: 1097-4652 (Electronic) 0021-9541 (Linking), (2011/34). @article{665b, title = {MicroRNAs facilitate skeletal muscle maintenance and metabolic suppression in hibernating brown bears}, author = {B E Luu and E Lefai and S Giroud and J E Swenson and B Chazarin and G Gauquelin-Koch and J M Arnemo and A L Evans and F Bertile and K B Storey}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31643088}, doi = {10.1002/jcp.29294}, issn = {1097-4652 (Electronic) 0021-9541 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {J Cell Physiol}, volume = {235}, number = {4}, pages = {3984-3993}, note = {2011/34}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Perraud, Q; Cantero, P; Roche, B; Gasser, V; Normant, V P; Kuhn, L; Hammann, P; Mislin, G L A; Ehret-Sabatier, L; Schalk, I J Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms Article de journal Mol Cell Proteomics, 19 (4), p. 589-607, 2020, ISSN: 1535-9484 (Electronic) 1535-9476 (Linking), (2015/28). @article{662, title = {Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms}, author = {Q Perraud and P Cantero and B Roche and V Gasser and V P Normant and L Kuhn and P Hammann and G L A Mislin and L Ehret-Sabatier and I J Schalk}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32024770}, doi = {10.1074/mcp.RA119.001829}, issn = {1535-9484 (Electronic) 1535-9476 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Mol Cell Proteomics}, volume = {19}, number = {4}, pages = {589-607}, note = {2015/28}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Postic, G; Marcoux, J; Reys, V; Andreani, J; Vandenbrouck, Y; Bousquet, M P; Mouton-Barbosa, E; Cianferani, S; Burlet-Schiltz, O; Guerois, R; Labesse, G; Tuffery, P Probing Protein Interaction Networks by Combining MS-Based Proteomics and Structural Data Integration Article de journal J Proteome Res, 19 (7), p. 2807-2820, 2020, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking), (pas de projet, pas de manips au labo). @article{669b, title = {Probing Protein Interaction Networks by Combining MS-Based Proteomics and Structural Data Integration}, author = {G Postic and J Marcoux and V Reys and J Andreani and Y Vandenbrouck and M P Bousquet and E Mouton-Barbosa and S Cianferani and O Burlet-Schiltz and R Guerois and G Labesse and P Tuffery}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32338910}, doi = {10.1021/acs.jproteome.0c00066}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {J Proteome Res}, volume = {19}, number = {7}, pages = {2807-2820}, note = {pas de projet, pas de manips au labo}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Sabou, M; Doderer-Lang, C; Leyer, C; Konjic, A; Kubina, S; Lennon, S; Rohr, O; Viville, S; Cianferani, S; Candolfi, E; Pfaff, A W; Brunet, J Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways Article de journal Cell Mol Life Sci, 77 (11), p. 2141-2156, 2020, ISSN: 1420-9071 (Electronic) 1420-682X (Linking). @article{670b, title = {Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways}, author = {M Sabou and C Doderer-Lang and C Leyer and A Konjic and S Kubina and S Lennon and O Rohr and S Viville and S Cianferani and E Candolfi and A W Pfaff and J Brunet}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31492965}, doi = {10.1007/s00018-019-03267-2}, issn = {1420-9071 (Electronic) 1420-682X (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Cell Mol Life Sci}, volume = {77}, number = {11}, pages = {2141-2156}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Sornay, C; Hessmann, S; Erb, S; Dovgan, I; Ehkirch, A; Botzanowski, T; Cianferani, S; Wagner, A; Chaubet, G Investigating Ugi / Passerini multicomponent reactions for the Site-Selective Conjugation of Native Trastuzumab Article de journal Chemistry, 2020, ISSN: 1521-3765 (Electronic) 0947-6539 (Linking), (2018/30). @article{671b, title = {Investigating Ugi / Passerini multicomponent reactions for the Site-Selective Conjugation of Native Trastuzumab}, author = {C Sornay and S Hessmann and S Erb and I Dovgan and A Ehkirch and T Botzanowski and S Cianferani and A Wagner and G Chaubet}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32588934}, doi = {10.1002/chem.202002432}, issn = {1521-3765 (Electronic) 0947-6539 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Chemistry}, note = {2018/30}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Spenle, C; Loustau, T; Murdamoothoo, D; Erne, W; la Divonne, Beghelli-de Forest S; Veber, R; Petti, L; Bourdely, P; Morgelin, M; Brauchle, E M; Cremel, G; Randrianarisoa, V; Camara, A; Rekima, S; Schaub, S; Nouhen, K; Imhof, T; Hansen, U; Paul, N; Carapito, R; Pythoud, N; Hirschler, A; Carapito, C; Dumortier, H; Mueller, C G; Koch, M; Schenke-Layland, K; Kon, S; Sudaka, A; Anjuere, F; Obberghen-Schilling, Van E; Orend, G Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma Article de journal Cancer Immunol Res, 2020, ISSN: 2326-6074 (Electronic) 2326-6066 (Linking), (????). @article{677, title = {Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma}, author = {C Spenle and T Loustau and D Murdamoothoo and W Erne and S Beghelli-de la Forest Divonne and R Veber and L Petti and P Bourdely and M Morgelin and E M Brauchle and G Cremel and V Randrianarisoa and A Camara and S Rekima and S Schaub and K Nouhen and T Imhof and U Hansen and N Paul and R Carapito and N Pythoud and A Hirschler and C Carapito and H Dumortier and C G Mueller and M Koch and K Schenke-Layland and S Kon and A Sudaka and F Anjuere and E Van Obberghen-Schilling and G Orend}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32665262}, doi = {10.1158/2326-6066.CIR-20-0074}, issn = {2326-6074 (Electronic) 2326-6066 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Cancer Immunol Res}, note = {????}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Tessier, R; Nandi, R K; Dwyer, B G; Abegg, D; Sornay, C; Ceballos, J; Erb, S; Cianferani, S; Wagner, A; Chaubet, G; Adibekian, A; Waser, J Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells Article de journal Angew Chem Int Ed Engl, 59 (27), p. 10961-10970, 2020, ISSN: 1521-3773 (Electronic) 1433-7851 (Linking). @article{672b, title = {Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells}, author = {R Tessier and R K Nandi and B G Dwyer and D Abegg and C Sornay and J Ceballos and S Erb and S Cianferani and A Wagner and G Chaubet and A Adibekian and J Waser}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32233093}, doi = {10.1002/anie.202002626}, issn = {1521-3773 (Electronic) 1433-7851 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Angew Chem Int Ed Engl}, volume = {59}, number = {27}, pages = {10961-10970}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Thompson, D; Cognat, V; Goodfellow, M; Koechler, S; Heintz, D; Carapito, C; Dorsselaer, Van A; Mahmoud, H; Sangal, V; Ismail, W Phylogenomic Classification and Biosynthetic Potential of the Fossil Fuel-Biodesulfurizing Rhodococcus Strain IGTS8 Article de journal Front Microbiol, 11 , p. 1417, 2020, ISSN: 1664-302X (Print) 1664-302X (Linking), (???). @article{676, title = {Phylogenomic Classification and Biosynthetic Potential of the Fossil Fuel-Biodesulfurizing Rhodococcus Strain IGTS8}, author = {D Thompson and V Cognat and M Goodfellow and S Koechler and D Heintz and C Carapito and A Van Dorsselaer and H Mahmoud and V Sangal and W Ismail}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32733398}, doi = {10.3389/fmicb.2020.01417}, issn = {1664-302X (Print) 1664-302X (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Front Microbiol}, volume = {11}, pages = {1417}, note = {???}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Wagner, E; Colas, O; Chenu, S; Goyon, A; Murisier, A; Cianferani, S; Francois, Y; Fekete, S; Guillarme, D; D'Atri, V; Beck, A Determination of size variants by CE-SDS for approved therapeutic antibodies: Key implications of subclasses and light chain specificities Article de journal J Pharm Biomed Anal, 184 , p. 113166, 2020, ISSN: 1873-264X (Electronic) 0731-7085 (Linking), (pas de manip MS). @article{642, title = {Determination of size variants by CE-SDS for approved therapeutic antibodies: Key implications of subclasses and light chain specificities}, author = {E Wagner and O Colas and S Chenu and A Goyon and A Murisier and S Cianferani and Y Francois and S Fekete and D Guillarme and V D'Atri and A Beck}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32113118}, doi = {10.1016/j.jpba.2020.113166}, issn = {1873-264X (Electronic) 0731-7085 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {J Pharm Biomed Anal}, volume = {184}, pages = {113166}, note = {pas de manip MS}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Wagner-Rousset, E; Colas, O; Francois, Y N; Heinisch, S; Guillarme, D; Cianferani, S; Beck, A Drug Loading and Distribution of ADCs After Reduction or IdeS Digestion and Reduction Article de journal Methods Mol Biol, 2078 , p. 187-195, 2020, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking), (pas de manip MS LSMBO). @article{660, title = {Drug Loading and Distribution of ADCs After Reduction or IdeS Digestion and Reduction}, author = {E Wagner-Rousset and O Colas and Y N Francois and S Heinisch and D Guillarme and S Cianferani and A Beck}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31643057}, doi = {10.1007/978-1-4939-9929-3_12}, issn = {1940-6029 (Electronic) 1064-3745 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Methods Mol Biol}, volume = {2078}, pages = {187-195}, note = {pas de manip MS LSMBO}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Bonnet, M; Soulat, J; Bons, J; Leger, S; Koning, De L; Carapito, C; Picard, B Quantification of biomarkers for beef meat qualities using a combination of Parallel Reaction Monitoring- and antibody-based proteomics Article de journal Food Chem, 317 , p. 126376, 2020, ISSN: 1873-7072 (Electronic) 0308-8146 (Linking), (???). @article{641b, title = {Quantification of biomarkers for beef meat qualities using a combination of Parallel Reaction Monitoring- and antibody-based proteomics}, author = {M Bonnet and J Soulat and J Bons and S Leger and L De Koning and C Carapito and B Picard}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32078991}, doi = {10.1016/j.foodchem.2020.126376}, issn = {1873-7072 (Electronic) 0308-8146 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Food Chem}, volume = {317}, pages = {126376}, abstract = {We and others have identified biomarker candidates of tenderness or marbling, two major attributes of bovine meat-eating qualities for consumers' satisfaction. In this study, Reverse Phase Protein Arrays (RPPA) and targeted mass spectrometry assays using Parallel Reaction Monitoring (PRM) were developed to test whether 10 proteins pass the sequential qualification and verification steps of the challenging biomarker discovery pipeline. At least MYH1, TPI1, ALDH1A1 and CRYAB were qualified by RPPA or PRM as being differentially abundant according to marbling values of longissimus thoracis and semimembranosus muscles. Significant mathematical relationships between the individual abundance of each of the four proteins and marbling values were verified by linear or logistic regressions. Four proteins, TNNT1, MDH1, PRDX6 and ENO3 were qualified and verified for tenderness, and the abundance of MDH1 explained 49% of the tenderness variability. The present PRM and RPPA results pave the way for development of useful meat industrial multiplex-proteins assays.}, note = {???}, keywords = {}, pubstate = {published}, tppubtype = {article} } We and others have identified biomarker candidates of tenderness or marbling, two major attributes of bovine meat-eating qualities for consumers' satisfaction. In this study, Reverse Phase Protein Arrays (RPPA) and targeted mass spectrometry assays using Parallel Reaction Monitoring (PRM) were developed to test whether 10 proteins pass the sequential qualification and verification steps of the challenging biomarker discovery pipeline. At least MYH1, TPI1, ALDH1A1 and CRYAB were qualified by RPPA or PRM as being differentially abundant according to marbling values of longissimus thoracis and semimembranosus muscles. Significant mathematical relationships between the individual abundance of each of the four proteins and marbling values were verified by linear or logistic regressions. Four proteins, TNNT1, MDH1, PRDX6 and ENO3 were qualified and verified for tenderness, and the abundance of MDH1 explained 49% of the tenderness variability. The present PRM and RPPA results pave the way for development of useful meat industrial multiplex-proteins assays. |
Ibrahim, M; Ayoub, D; Wasselin, T; Dorsselaer, Van A; Maho, Le Y; Raclot, T; Bertile, F Alterations in rat adipose tissue transcriptome and proteome in response to prolonged fasting. Article de journal Biological Chemistry, 401 (3), p. 389-405, 2020, (2009/41). @article{643b, title = {Alterations in rat adipose tissue transcriptome and proteome in response to prolonged fasting.}, author = {M Ibrahim and D Ayoub and T Wasselin and A Van Dorsselaer and Y Le Maho and T Raclot and F Bertile}, year = {2020}, date = {2020-01-01}, journal = {Biological Chemistry}, volume = {401}, number = {3}, pages = {389-405}, note = {2009/41}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Belorusova, A Y; Bourguet, M; Hessmann, S; Chalhoub, S; Kieffer, B; Cianferani, S; Rochel, N Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer Article de journal Nucleic Acids Res, 48 (19), p. 11199-11213, 2020, ISSN: 1362-4962 (Electronic) 0305-1048 (Linking), (Belorusova, Anna Y Bourguet, Maxime Hessmann, Steve Chalhoub, Sandra Kieffer, Bruno Cianferani, Sarah Rochel, Natacha eng Research Support, Non-U.S. Gov't England 2020/09/30 06:00 Nucleic Acids Res. 2020 Nov 4;48(19):11199-11213. doi: 10.1093/nar/gkaa775.). @article{691, title = {Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer}, author = {A Y Belorusova and M Bourguet and S Hessmann and S Chalhoub and B Kieffer and S Cianferani and N Rochel}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32990725}, doi = {10.1093/nar/gkaa775}, issn = {1362-4962 (Electronic) 0305-1048 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Nucleic Acids Res}, volume = {48}, number = {19}, pages = {11199-11213}, abstract = {The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with the structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes.}, note = {Belorusova, Anna Y Bourguet, Maxime Hessmann, Steve Chalhoub, Sandra Kieffer, Bruno Cianferani, Sarah Rochel, Natacha eng Research Support, Non-U.S. Gov't England 2020/09/30 06:00 Nucleic Acids Res. 2020 Nov 4;48(19):11199-11213. doi: 10.1093/nar/gkaa775.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with the structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes. |
Bernard, Q; Grillon, A; Lenormand, C; Ehret-Sabatier, L; Boulanger, N Skin Interface, a Key Player for Borrelia Multiplication and Persistence in Lyme Borreliosis Article de journal Trends Parasitol, 36 (3), p. 304-314, 2020, ISSN: 1471-5007 (Electronic) 1471-4922 (Linking), (2012/30). @article{654, title = {Skin Interface, a Key Player for Borrelia Multiplication and Persistence in Lyme Borreliosis}, author = {Q Bernard and A Grillon and C Lenormand and L Ehret-Sabatier and N Boulanger}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32007396}, doi = {10.1016/j.pt.2019.12.017}, issn = {1471-5007 (Electronic) 1471-4922 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Trends Parasitol}, volume = {36}, number = {3}, pages = {304-314}, abstract = {The skin plays a key role in vector-borne diseases because it is the site where the arthropod coinoculates pathogens and its saliva. Lyme borreliosis, particularly well investigated in this context, is a multisystemic infectious disease caused by Borrelia burgdorferi sensu lato and transmitted by the hard tick Ixodes. Numerous in vitro studies were conducted to better understand the role of specific skin cells and tick saliva in host defense, vector feeding, and pathogen transmission. The skin was also evidenced in various animal models as the site of bacterial multiplication and persistence. We present the achievements in this field as well as the gaps that impede comprehensive knowledge of the disease pathophysiology and the development of efficient diagnostic tools and vaccines in humans.}, note = {2012/30}, keywords = {}, pubstate = {published}, tppubtype = {article} } The skin plays a key role in vector-borne diseases because it is the site where the arthropod coinoculates pathogens and its saliva. Lyme borreliosis, particularly well investigated in this context, is a multisystemic infectious disease caused by Borrelia burgdorferi sensu lato and transmitted by the hard tick Ixodes. Numerous in vitro studies were conducted to better understand the role of specific skin cells and tick saliva in host defense, vector feeding, and pathogen transmission. The skin was also evidenced in various animal models as the site of bacterial multiplication and persistence. We present the achievements in this field as well as the gaps that impede comprehensive knowledge of the disease pathophysiology and the development of efficient diagnostic tools and vaccines in humans. |
Boyer, C; Cussonneau, L; Brun, C; Deval, C; de Barros, Pais J P; Chanon, S; Bernoud-Hubac, N; Daira, P; Evans, A L; Arnemo, J M; Swenson, J E; Gauquelin-Koch, G; Simon, C; Blanc, S; Combaret, L; Bertile, F; Lefai, E Specific shifts in the endocannabinoid system in hibernating brown bears Article de journal Front Zool, 17 (1), p. 35, 2020, ISSN: 1742-9994 (Print) 1742-9994 (Linking), (2011/34). @article{680, title = {Specific shifts in the endocannabinoid system in hibernating brown bears}, author = {C Boyer and L Cussonneau and C Brun and C Deval and J P Pais de Barros and S Chanon and N Bernoud-Hubac and P Daira and A L Evans and J M Arnemo and J E Swenson and G Gauquelin-Koch and C Simon and S Blanc and L Combaret and F Bertile and E Lefai}, url = {https://www.ncbi.nlm.nih.gov/pubmed/33292302}, doi = {10.1186/s12983-020-00380-y}, issn = {1742-9994 (Print) 1742-9994 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Front Zool}, volume = {17}, number = {1}, pages = {35}, abstract = {In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear's peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.}, note = {2011/34}, keywords = {}, pubstate = {published}, tppubtype = {article} } In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear's peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment. |
Dalzon, B; Aude-Garcia, C; Diemer, H; Bons, J; Marie-Desvergne, C; Perard, J; Dubosson, M; Collin-Faure, V; Carapito, C; Sanglier-Cianferani, S; Carriere, M; Rabilloud, T The longer the worse: a combined proteomic and targeted study of the long-termversusshort-term effects of silver nanoparticles on macrophages Article de journal Environmental Science-Nano, 7 (7), p. 2032-2046, 2020, ISSN: 2051-8153, (2014/29). @article{694, title = {The longer the worse: a combined proteomic and targeted study of the long-termversusshort-term effects of silver nanoparticles on macrophages}, author = {B Dalzon and C Aude-Garcia and H Diemer and J Bons and C Marie-Desvergne and J Perard and M Dubosson and V Collin-Faure and C Carapito and S Sanglier-Cianferani and M Carriere and T Rabilloud}, url = {<Go to ISI>://WOS:000549099000010}, doi = {10.1039/c9en01329f}, issn = {2051-8153}, year = {2020}, date = {2020-01-01}, journal = {Environmental Science-Nano}, volume = {7}, number = {7}, pages = {2032-2046}, abstract = {Despite considerable research effort devoted to the study of the effects of silver nanoparticles on mammalian cells in recent years, data on the potential long term effects of this nanomaterial remain scarce, and centered on epithelial cells. The aim of this study was to explore the effects of silver nanoparticles on macrophages. To this end, RAW 264.7 murine macrophages were exposed to either 1 mu g ml(-1)silver nanoparticles for 20 days,i.e.a chronic exposure scheme, or to 20 mu g ml(-1)silver nanoparticles for 24 hours,i.e.an acute exposure scheme. A proteomic study was then conducted to study and compare the cellular responses to both exposure schemes. They proved to be essentially different, and stronger for the chronic exposure scheme. Targeted validation studies showed effects of chronic exposure to silver nanoparticles on detoxifying enzymes such as flavin reductase, which was increased, and on central metabolism enzymes such as triose phosphate isomerase, the activity of which decreased under chronic exposure to silver nanoparticles. Chronic exposure to silver nanoparticles also induced a decrease of reduced glutathione content, a decreased phagocytic activity and reduced macrophage responses to lipopolysaccharide, as exemplified by nitric oxide and interleukin 6 production. Overall, chronic exposure to silver nanoparticles induced stronger effects than acute exposure on macrophages in the metabolic (glutathione level, mitochondrial potential) and functional (phagocytosis, cytokine production) parameters tested.}, note = {2014/29}, keywords = {}, pubstate = {published}, tppubtype = {article} } Despite considerable research effort devoted to the study of the effects of silver nanoparticles on mammalian cells in recent years, data on the potential long term effects of this nanomaterial remain scarce, and centered on epithelial cells. The aim of this study was to explore the effects of silver nanoparticles on macrophages. To this end, RAW 264.7 murine macrophages were exposed to either 1 mu g ml(-1)silver nanoparticles for 20 days,i.e.a chronic exposure scheme, or to 20 mu g ml(-1)silver nanoparticles for 24 hours,i.e.an acute exposure scheme. A proteomic study was then conducted to study and compare the cellular responses to both exposure schemes. They proved to be essentially different, and stronger for the chronic exposure scheme. Targeted validation studies showed effects of chronic exposure to silver nanoparticles on detoxifying enzymes such as flavin reductase, which was increased, and on central metabolism enzymes such as triose phosphate isomerase, the activity of which decreased under chronic exposure to silver nanoparticles. Chronic exposure to silver nanoparticles also induced a decrease of reduced glutathione content, a decreased phagocytic activity and reduced macrophage responses to lipopolysaccharide, as exemplified by nitric oxide and interleukin 6 production. Overall, chronic exposure to silver nanoparticles induced stronger effects than acute exposure on macrophages in the metabolic (glutathione level, mitochondrial potential) and functional (phagocytosis, cytokine production) parameters tested. |
Desligniere, E; Ehkirch, A; Botzanowski, T; Beck, A; Hernandez-Alba, O; Cianferani, S Toward Automation of Collision-Induced Unfolding Experiments through Online Size Exclusion Chromatography Coupled to Native Mass Spectrometry Article de journal Anal Chem, 92 (19), p. 12900-12908, 2020, ISSN: 1520-6882 (Electronic) 0003-2700 (Linking), (Desligniere, Evolene Ehkirch, Anthony Botzanowski, Thomas Beck, Alain Hernandez-Alba, Oscar Cianferani, Sarah eng Research Support, Non-U.S. Gov't 2020/09/05 06:00 Anal Chem. 2020 Oct 6;92(19):12900-12908. doi: 10.1021/acs.analchem.0c01426. Epub 2020 Sep 18.). @article{690, title = {Toward Automation of Collision-Induced Unfolding Experiments through Online Size Exclusion Chromatography Coupled to Native Mass Spectrometry}, author = {E Desligniere and A Ehkirch and T Botzanowski and A Beck and O Hernandez-Alba and S Cianferani}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32886492}, doi = {10.1021/acs.analchem.0c01426}, issn = {1520-6882 (Electronic) 0003-2700 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Anal Chem}, volume = {92}, number = {19}, pages = {12900-12908}, abstract = {Ion mobility (IM)-based collision-induced unfolding (CIU) has gained increasing attention to probe gas-phase unfolding of proteins and their noncovalent complexes, notably for biotherapeutics. CIU detects subtle conformational changes of proteins and emerges as an attractive alternative to circumvent poor IM resolution. However, CIU still lacks in automation for buffer exchange and data acquisition, precluding its wide adoption. We present here an automated workflow for CIU experiments, from sample preparation to data interpretation using online size exclusion chromatography coupled to native IM mass spectrometry (SEC-CIU). Online automated SEC-CIU experiments offer several benefits over nanoESI-CIU, among which are (i) improved and fast desalting compared to manual buffer exchange used for classical CIU experiments; (ii) drastic reduction of the overall data collection time process; and (iii) maintaining the number of unfolding transitions. We then evaluate the potential of SEC-CIU to distinguish monoclonal antibody (mAb) subclasses, illustrating the efficiency of our method for rapid mAb subclass identification at both intact and middle levels. Finally, we demonstrate that CIU data acquisition time can be further reduced either by setting up a scheduled CIU method relying on diagnostic trap collision voltages or by implementing mAb-multiplexed SEC-CIU analyses to maximize information content in a single experiment. Altogether, our results confirm the suitability of SEC-CIU to automate CIU experiments, particularly for the fast characterization of next-generation mAb-based products.}, note = {Desligniere, Evolene Ehkirch, Anthony Botzanowski, Thomas Beck, Alain Hernandez-Alba, Oscar Cianferani, Sarah eng Research Support, Non-U.S. Gov't 2020/09/05 06:00 Anal Chem. 2020 Oct 6;92(19):12900-12908. doi: 10.1021/acs.analchem.0c01426. Epub 2020 Sep 18.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Ion mobility (IM)-based collision-induced unfolding (CIU) has gained increasing attention to probe gas-phase unfolding of proteins and their noncovalent complexes, notably for biotherapeutics. CIU detects subtle conformational changes of proteins and emerges as an attractive alternative to circumvent poor IM resolution. However, CIU still lacks in automation for buffer exchange and data acquisition, precluding its wide adoption. We present here an automated workflow for CIU experiments, from sample preparation to data interpretation using online size exclusion chromatography coupled to native IM mass spectrometry (SEC-CIU). Online automated SEC-CIU experiments offer several benefits over nanoESI-CIU, among which are (i) improved and fast desalting compared to manual buffer exchange used for classical CIU experiments; (ii) drastic reduction of the overall data collection time process; and (iii) maintaining the number of unfolding transitions. We then evaluate the potential of SEC-CIU to distinguish monoclonal antibody (mAb) subclasses, illustrating the efficiency of our method for rapid mAb subclass identification at both intact and middle levels. Finally, we demonstrate that CIU data acquisition time can be further reduced either by setting up a scheduled CIU method relying on diagnostic trap collision voltages or by implementing mAb-multiplexed SEC-CIU analyses to maximize information content in a single experiment. Altogether, our results confirm the suitability of SEC-CIU to automate CIU experiments, particularly for the fast characterization of next-generation mAb-based products. |
Ibrahim, M; Wasselin, T; Challet, E; Dorsselaer, Van A; Maho, Le Y; Raclot, T; Bertile, F Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats Article de journal Int J Mol Sci, 21 (17), 2020, ISSN: 1422-0067 (Electronic) 1422-0067 (Linking), (Ibrahim, Marianne Wasselin, Thierry Challet, Etienne Van Dorsselaer, Alain Le Maho, Yvon Raclot, Thierry Bertile, Fabrice eng ANR-05-BLAN-0069/Agence Nationale de la Recherche ANR-10-INSB-08-03/Proteomics French Infrastructure (ProFI) Switzerland 2020/08/23 06:00 Int J Mol Sci. 2020 Aug 20;21(17). pii: ijms21175984. doi: 10.3390/ijms21175984.). @article{681b, title = {Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats}, author = {M Ibrahim and T Wasselin and E Challet and A Van Dorsselaer and Y Le Maho and T Raclot and F Bertile}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32825252}, doi = {10.3390/ijms21175984}, issn = {1422-0067 (Electronic) 1422-0067 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Int J Mol Sci}, volume = {21}, number = {17}, abstract = {Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases.}, note = {Ibrahim, Marianne Wasselin, Thierry Challet, Etienne Van Dorsselaer, Alain Le Maho, Yvon Raclot, Thierry Bertile, Fabrice eng ANR-05-BLAN-0069/Agence Nationale de la Recherche ANR-10-INSB-08-03/Proteomics French Infrastructure (ProFI) Switzerland 2020/08/23 06:00 Int J Mol Sci. 2020 Aug 20;21(17). pii: ijms21175984. doi: 10.3390/ijms21175984.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases. |
Lacoux, C; Wacheul, L; Saraf, K; Pythoud, N; Huvelle, E; Figaro, S; Graille, M; Carapito, C; Lafontaine, D L J; Heurgue-Hamard, V The catalytic activity of the translation termination factor methyltransferase Mtq2-Trm112 complex is required for large ribosomal subunit biogenesis Article de journal Nucleic Acids Res, 48 (21), p. 12310-12325, 2020, ISSN: 1362-4962 (Electronic) 0305-1048 (Linking), (Lacoux, Caroline Wacheul, Ludivine Saraf, Kritika Pythoud, Nicolas Huvelle, Emmeline Figaro, Sabine Graille, Marc Carapito, Christine Lafontaine, Denis L J Heurgue-Hamard, Valerie eng Research Support, Non-U.S. Gov't England 2020/11/10 06:00 Nucleic Acids Res. 2020 Dec 2;48(21):12310-12325. doi: 10.1093/nar/gkaa972.). @article{693, title = {The catalytic activity of the translation termination factor methyltransferase Mtq2-Trm112 complex is required for large ribosomal subunit biogenesis}, author = {C Lacoux and L Wacheul and K Saraf and N Pythoud and E Huvelle and S Figaro and M Graille and C Carapito and D L J Lafontaine and V Heurgue-Hamard}, url = {https://www.ncbi.nlm.nih.gov/pubmed/33166396}, doi = {10.1093/nar/gkaa972}, issn = {1362-4962 (Electronic) 0305-1048 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Nucleic Acids Res}, volume = {48}, number = {21}, pages = {12310-12325}, abstract = {The Mtq2-Trm112 methyltransferase modifies the eukaryotic translation termination factor eRF1 on the glutamine side chain of a universally conserved GGQ motif that is essential for release of newly synthesized peptides. Although this modification is found in the three domains of life, its exact role in eukaryotes remains unknown. As the deletion of MTQ2 leads to severe growth impairment in yeast, we have investigated its role further and tested its putative involvement in ribosome biogenesis. We found that Mtq2 is associated with nuclear 60S subunit precursors, and we demonstrate that its catalytic activity is required for nucleolar release of pre-60S and for efficient production of mature 5.8S and 25S rRNAs. Thus, we identify Mtq2 as a novel ribosome assembly factor important for large ribosomal subunit formation. We propose that Mtq2-Trm112 might modify eRF1 in the nucleus as part of a quality control mechanism aimed at proof-reading the peptidyl transferase center, where it will subsequently bind during translation termination.}, note = {Lacoux, Caroline Wacheul, Ludivine Saraf, Kritika Pythoud, Nicolas Huvelle, Emmeline Figaro, Sabine Graille, Marc Carapito, Christine Lafontaine, Denis L J Heurgue-Hamard, Valerie eng Research Support, Non-U.S. Gov't England 2020/11/10 06:00 Nucleic Acids Res. 2020 Dec 2;48(21):12310-12325. doi: 10.1093/nar/gkaa972.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Mtq2-Trm112 methyltransferase modifies the eukaryotic translation termination factor eRF1 on the glutamine side chain of a universally conserved GGQ motif that is essential for release of newly synthesized peptides. Although this modification is found in the three domains of life, its exact role in eukaryotes remains unknown. As the deletion of MTQ2 leads to severe growth impairment in yeast, we have investigated its role further and tested its putative involvement in ribosome biogenesis. We found that Mtq2 is associated with nuclear 60S subunit precursors, and we demonstrate that its catalytic activity is required for nucleolar release of pre-60S and for efficient production of mature 5.8S and 25S rRNAs. Thus, we identify Mtq2 as a novel ribosome assembly factor important for large ribosomal subunit formation. We propose that Mtq2-Trm112 might modify eRF1 in the nucleus as part of a quality control mechanism aimed at proof-reading the peptidyl transferase center, where it will subsequently bind during translation termination. |
Launay, K; Amalian, J A; Laurent, E; Oswald, L; Ouahabi, Al A; Burel, A; Dufour, F; Carapito, C; Clement, J L; Lutz, J F; Charles, L; Gigmes, D Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s Article de journal Angew Chem Int Ed Engl, 2020, ISSN: 1521-3773 (Electronic) 1433-7851 (Linking), (Launay, Kevin Amalian, Jean-Arthur Laurent, Eline Oswald, Laurence Al Ouahabi, Abdelaziz Burel, Alexandre Dufour, Florent Carapito, Christine Clement, Jean-Louis Lutz, Jean-Francois Charles, Laurence Gigmes, Didier eng ANR-16-CE29-0004-01/Agence Nationale de la Recherche ANR-16-CE29-0004-02/Agence Nationale de la Recherche Germany 2020/09/24 06:00 Angew Chem Int Ed Engl. 2020 Sep 22. doi: 10.1002/anie.202010171.). @article{692, title = {Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s}, author = {K Launay and J A Amalian and E Laurent and L Oswald and A Al Ouahabi and A Burel and F Dufour and C Carapito and J L Clement and J F Lutz and L Charles and D Gigmes}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32964618}, doi = {10.1002/anie.202010171}, issn = {1521-3773 (Electronic) 1433-7851 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Angew Chem Int Ed Engl}, abstract = {A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub-segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side-products from the amide-based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side-reactions and enable automated MS/MS sequencing. Different styryl-TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in-chain benzyl ring, with no side-reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS-DECODER software, which interprets fragmentation data recorded for each sub-segment and re-align them in their original order based on location tags.}, note = {Launay, Kevin Amalian, Jean-Arthur Laurent, Eline Oswald, Laurence Al Ouahabi, Abdelaziz Burel, Alexandre Dufour, Florent Carapito, Christine Clement, Jean-Louis Lutz, Jean-Francois Charles, Laurence Gigmes, Didier eng ANR-16-CE29-0004-01/Agence Nationale de la Recherche ANR-16-CE29-0004-02/Agence Nationale de la Recherche Germany 2020/09/24 06:00 Angew Chem Int Ed Engl. 2020 Sep 22. doi: 10.1002/anie.202010171.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub-segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side-products from the amide-based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side-reactions and enable automated MS/MS sequencing. Different styryl-TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in-chain benzyl ring, with no side-reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS-DECODER software, which interprets fragmentation data recorded for each sub-segment and re-align them in their original order based on location tags. |
Nguyen, A; Nguyen, D; Nguyen, Phong T X; Sebastiani, M; Dorr, S; Hernandez-Alba, O; Debaene, F; Cianferani, S; Heine, A; Klebe, G; Reuter, K The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase Article de journal ACS Chem Biol, 15 (11), p. 3021-3029, 2020, ISSN: 1554-8937 (Electronic) 1554-8929 (Linking), (Nguyen, Andreas Nguyen, Dzung Phong Nguyen, Tran Xuan Sebastiani, Maurice Dorr, Stefanie Hernandez-Alba, Oscar Debaene, Francois Cianferani, Sarah Heine, Andreas Klebe, Gerhard Reuter, Klaus eng Research Support, Non-U.S. Gov't 2020/11/10 06:00 ACS Chem Biol. 2020 Nov 20;15(11):3021-3029. doi: 10.1021/acschembio.0c00700. Epub 2020 Nov 9.). @article{689b, title = {The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase}, author = {A Nguyen and D Nguyen and T X Phong Nguyen and M Sebastiani and S Dorr and O Hernandez-Alba and F Debaene and S Cianferani and A Heine and G Klebe and K Reuter}, url = {https://www.ncbi.nlm.nih.gov/pubmed/33166460}, doi = {10.1021/acschembio.0c00700}, issn = {1554-8937 (Electronic) 1554-8929 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {ACS Chem Biol}, volume = {15}, number = {11}, pages = {3021-3029}, abstract = {Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Therefore, Tgt constitutes a putative target for Shigellosis drug therapy. Since it is only active as homodimer, interference with dimer-interface formation may, in addition to active-site inhibition, provide further means to disable this protein. A cluster of four aromatic residues seems important to stabilize the homodimer. We mutated residues of this aromatic cluster and analyzed each mutated variant with respect to the dimer and thermal stability or enzyme activity by applying native mass spectrometry, a thermal shift assay, enzyme kinetics, and X-ray crystallography. Our structural studies indicate a strong influence of pH on the homodimer stability. Apparently, protonation of a histidine within the aromatic cluster supports the collapse of an essential structural motif within the dimer interface at slightly acidic pH.}, note = {Nguyen, Andreas Nguyen, Dzung Phong Nguyen, Tran Xuan Sebastiani, Maurice Dorr, Stefanie Hernandez-Alba, Oscar Debaene, Francois Cianferani, Sarah Heine, Andreas Klebe, Gerhard Reuter, Klaus eng Research Support, Non-U.S. Gov't 2020/11/10 06:00 ACS Chem Biol. 2020 Nov 20;15(11):3021-3029. doi: 10.1021/acschembio.0c00700. Epub 2020 Nov 9.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Therefore, Tgt constitutes a putative target for Shigellosis drug therapy. Since it is only active as homodimer, interference with dimer-interface formation may, in addition to active-site inhibition, provide further means to disable this protein. A cluster of four aromatic residues seems important to stabilize the homodimer. We mutated residues of this aromatic cluster and analyzed each mutated variant with respect to the dimer and thermal stability or enzyme activity by applying native mass spectrometry, a thermal shift assay, enzyme kinetics, and X-ray crystallography. Our structural studies indicate a strong influence of pH on the homodimer stability. Apparently, protonation of a histidine within the aromatic cluster supports the collapse of an essential structural motif within the dimer interface at slightly acidic pH. |
Oerum, S; Dendooven, T; Catala, M; Gilet, L; Degut, C; Trinquier, A; Bourguet, M; Barraud, P; Cianferani, S; Luisi, B F; Condon, C; Tisne, C Structures of B. subtilis Maturation RNases Captured on 50S Ribosome with Pre-rRNAs Article de journal Mol Cell, 80 (2), p. 227-236 e5, 2020, ISSN: 1097-4164 (Electronic) 1097-2765 (Linking), (Oerum, Stephanie Dendooven, Tom Catala, Marjorie Gilet, Laetitia Degut, Clement Trinquier, Aude Bourguet, Maxime Barraud, Pierre Cianferani, Sarah Luisi, Ben F Condon, Ciaran Tisne, Carine eng 206171/Z/17/Z/WT_/Wellcome Trust/United Kingdom 202905/Z/16/Z/WT_/Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't 2020/09/30 06:00 Mol Cell. 2020 Oct 15;80(2):227-236.e5. doi: 10.1016/j.molcel.2020.09.008. Epub 2020 Sep 28.). @article{688, title = {Structures of B. subtilis Maturation RNases Captured on 50S Ribosome with Pre-rRNAs}, author = {S Oerum and T Dendooven and M Catala and L Gilet and C Degut and A Trinquier and M Bourguet and P Barraud and S Cianferani and B F Luisi and C Condon and C Tisne}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32991829}, doi = {10.1016/j.molcel.2020.09.008}, issn = {1097-4164 (Electronic) 1097-2765 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Mol Cell}, volume = {80}, number = {2}, pages = {227-236 e5}, abstract = {The pathways for ribosomal RNA (rRNA) maturation diverge greatly among the domains of life. In the Gram-positive model bacterium, Bacillus subtilis, the final maturation steps of the two large ribosomal subunit (50S) rRNAs, 23S and 5S pre-rRNAs, are catalyzed by the double-strand specific ribonucleases (RNases) Mini-RNase III and RNase M5, respectively. Here we present a protocol that allowed us to solve the 3.0 and 3.1 A resolution cryoelectron microscopy structures of these RNases poised to cleave their pre-rRNA substrates within the B. subtilis 50S particle. These data provide the first structural insights into rRNA maturation in bacteria by revealing how these RNases recognize and process double-stranded pre-rRNA. Our structures further uncover how specific ribosomal proteins act as chaperones to correctly fold the pre-rRNA substrates and, for Mini-III, anchor the RNase to the ribosome. These r-proteins thereby serve a quality-control function in the process from accurate ribosome assembly to rRNA processing.}, note = {Oerum, Stephanie Dendooven, Tom Catala, Marjorie Gilet, Laetitia Degut, Clement Trinquier, Aude Bourguet, Maxime Barraud, Pierre Cianferani, Sarah Luisi, Ben F Condon, Ciaran Tisne, Carine eng 206171/Z/17/Z/WT_/Wellcome Trust/United Kingdom 202905/Z/16/Z/WT_/Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't 2020/09/30 06:00 Mol Cell. 2020 Oct 15;80(2):227-236.e5. doi: 10.1016/j.molcel.2020.09.008. Epub 2020 Sep 28.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The pathways for ribosomal RNA (rRNA) maturation diverge greatly among the domains of life. In the Gram-positive model bacterium, Bacillus subtilis, the final maturation steps of the two large ribosomal subunit (50S) rRNAs, 23S and 5S pre-rRNAs, are catalyzed by the double-strand specific ribonucleases (RNases) Mini-RNase III and RNase M5, respectively. Here we present a protocol that allowed us to solve the 3.0 and 3.1 A resolution cryoelectron microscopy structures of these RNases poised to cleave their pre-rRNA substrates within the B. subtilis 50S particle. These data provide the first structural insights into rRNA maturation in bacteria by revealing how these RNases recognize and process double-stranded pre-rRNA. Our structures further uncover how specific ribosomal proteins act as chaperones to correctly fold the pre-rRNA substrates and, for Mini-III, anchor the RNase to the ribosome. These r-proteins thereby serve a quality-control function in the process from accurate ribosome assembly to rRNA processing. |
Osz, J; McEwen, A G; Bourguet, M; Przybilla, F; Peluso-Iltis, C; Poussin-Courmontagne, P; Mely, Y; Cianferani, S; Jeffries, C M; Svergun, D I; Rochel, N Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR-RXR Article de journal Nucleic Acids Res, 48 (17), p. 9969-9985, 2020, ISSN: 1362-4962 (Electronic) 0305-1048 (Linking), (Osz, Judit McEwen, Alastair G Bourguet, Maxime Przybilla, Frederic Peluso-Iltis, Carole Poussin-Courmontagne, Pierre Mely, Yves Cianferani, Sarah Jeffries, Cy M Svergun, Dmitri I Rochel, Natacha eng Research Support, Non-U.S. Gov't England 2020/09/26 06:00 Nucleic Acids Res. 2020 Sep 25;48(17):9969-9985. doi: 10.1093/nar/gkaa697.). @article{687, title = {Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR-RXR}, author = {J Osz and A G McEwen and M Bourguet and F Przybilla and C Peluso-Iltis and P Poussin-Courmontagne and Y Mely and S Cianferani and C M Jeffries and D I Svergun and N Rochel}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32974652}, doi = {10.1093/nar/gkaa697}, issn = {1362-4962 (Electronic) 0305-1048 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Nucleic Acids Res}, volume = {48}, number = {17}, pages = {9969-9985}, abstract = {Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insights for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structures of RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR-RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding modes between DR0 and DR5 were observed leading to differences in conformation and structural dynamics of the multi-domain RXR-RAR DNA complexes. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR-RAR heterodimers.}, note = {Osz, Judit McEwen, Alastair G Bourguet, Maxime Przybilla, Frederic Peluso-Iltis, Carole Poussin-Courmontagne, Pierre Mely, Yves Cianferani, Sarah Jeffries, Cy M Svergun, Dmitri I Rochel, Natacha eng Research Support, Non-U.S. Gov't England 2020/09/26 06:00 Nucleic Acids Res. 2020 Sep 25;48(17):9969-9985. doi: 10.1093/nar/gkaa697.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insights for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structures of RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR-RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding modes between DR0 and DR5 were observed leading to differences in conformation and structural dynamics of the multi-domain RXR-RAR DNA complexes. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR-RAR heterodimers. |
Talagrand-Reboul, E; Westermann, B; Raess, M A; Schnell, G; Cantero, P; Barthel, C; Ehret-Sabatier, L; Jaulhac, B; Boulanger, N Proteomic as an Exploratory Approach to Develop Vaccines Against Tick-Borne Diseases Using Lyme Borreliosis as a Test Case Article de journal Vaccines (Basel), 8 (3), 2020, ISSN: 2076-393X (Print) 2076-393X (Linking), (2012-31). @article{683b, title = {Proteomic as an Exploratory Approach to Develop Vaccines Against Tick-Borne Diseases Using Lyme Borreliosis as a Test Case}, author = {E Talagrand-Reboul and B Westermann and M A Raess and G Schnell and P Cantero and C Barthel and L Ehret-Sabatier and B Jaulhac and N Boulanger}, url = {https://www.ncbi.nlm.nih.gov/pubmed/32825641}, doi = {10.3390/vaccines8030463}, issn = {2076-393X (Print) 2076-393X (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Vaccines (Basel)}, volume = {8}, number = {3}, abstract = {Tick-borne diseases affecting humans and animals are on the rise worldwide. Vaccines constitute an effective control measure, but very few are available. We selected Lyme borreliosis, a bacterial infection transmitted by the hard tick Ixodes, to validate a new concept to identify vaccine candidates. This disease is the most common tick-borne disease in the Northern Hemisphere. Although attempts to develop a vaccine exist, none have been successfully marketed. In tick-borne diseases, the skin constitutes a very specific environment encountered by the pathogen during its co-inoculation with tick saliva. In a mouse model, we developed a proteomic approach to identify vaccine candidates in skin biopsies. We identified 30 bacterial proteins after syringe inoculation or tick inoculation of bacteria. Discovery proteomics using mass spectrometry might be used in various tick-borne diseases to identify pathogen proteins with early skin expression. It should help to better develop sub-unit vaccines based on a cocktail of several antigens, associated with effective adjuvant and delivery systems of antigens. In all vector-borne diseases, the skin deserves further investigation to better define its role in the elaboration of protective immunity against pathogens.}, note = {2012-31}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tick-borne diseases affecting humans and animals are on the rise worldwide. Vaccines constitute an effective control measure, but very few are available. We selected Lyme borreliosis, a bacterial infection transmitted by the hard tick Ixodes, to validate a new concept to identify vaccine candidates. This disease is the most common tick-borne disease in the Northern Hemisphere. Although attempts to develop a vaccine exist, none have been successfully marketed. In tick-borne diseases, the skin constitutes a very specific environment encountered by the pathogen during its co-inoculation with tick saliva. In a mouse model, we developed a proteomic approach to identify vaccine candidates in skin biopsies. We identified 30 bacterial proteins after syringe inoculation or tick inoculation of bacteria. Discovery proteomics using mass spectrometry might be used in various tick-borne diseases to identify pathogen proteins with early skin expression. It should help to better develop sub-unit vaccines based on a cocktail of several antigens, associated with effective adjuvant and delivery systems of antigens. In all vector-borne diseases, the skin deserves further investigation to better define its role in the elaboration of protective immunity against pathogens. |
Torres, A; Dalzon, B; Collin-Faure, V; Diemer, H; Fenel, D; Schoehn, G; Cianferani, S; Carriere, M; Rabilloud, T How Reversible Are the Effects of Fumed Silica on Macrophages? A Proteomics-Informed View Article de journal Nanomaterials (Basel), 10 (10), 2020, ISSN: 2079-4991 (Print) 2079-4991 (Linking), (Torres, Anaelle Dalzon, Bastien Collin-Faure, Veronique Diemer, Helene Fenel, Daphna Schoehn, Guy Cianferani, Sarah Carriere, Marie Rabilloud, Thierry eng PNREST 2015/032/Agence Nationale de Securite Sanitaire de l'Alimentation, de l'Environnement et du Travail ANR-16-CE34-0011; ANR-11-LABX-0064; ANR-10-INBS-05-02; ANR-17-EURE-0003; ANR-10-INBS-08-03/Agence Nationale de la Recherche Switzerland 2020/10/03 06:00 Nanomaterials (Basel). 2020 Sep 29;10(10). pii: nano10101939. doi: 10.3390/nano10101939.). @article{685, title = {How Reversible Are the Effects of Fumed Silica on Macrophages? A Proteomics-Informed View}, author = {A Torres and B Dalzon and V Collin-Faure and H Diemer and D Fenel and G Schoehn and S Cianferani and M Carriere and T Rabilloud}, url = {https://www.ncbi.nlm.nih.gov/pubmed/33003391}, doi = {10.3390/nano10101939}, issn = {2079-4991 (Print) 2079-4991 (Linking)}, year = {2020}, date = {2020-01-01}, journal = {Nanomaterials (Basel)}, volume = {10}, number = {10}, abstract = {Synthetic amorphous silica is one of the most used nanomaterials, and numerous toxicological studies have studied its effects. Most of these studies have used an acute exposure mode to investigate the effects immediately after exposure. However, this exposure modality does not allow the investigation of the persistence of the effects, which is a crucial aspect of silica toxicology, as exemplified by crystalline silica. In this paper, we extended the investigations by studying not only the responses immediately after exposure but also after a 72 h post-exposure recovery phase. We used a pyrolytic silica as the test nanomaterial, as this variant of synthetic amorphous silica has been shown to induce a more persistent inflammation in vivo than precipitated silica. To investigate macrophage responses to pyrolytic silica, we used a combination of proteomics and targeted experiments, which allowed us to show that most of the cellular functions that were altered immediately after exposure to pyrolytic silica at a subtoxic dose, such as energy metabolism and cell morphology, returned to normal at the end of the recovery period. However, some alterations, such as the inflammatory responses and some aldehyde detoxification proteins, were persistent. At the proteomic level, other alterations, such as proteins implicated in the endosomal/lysosomal pathway, were also persistent but resulted in normal function, thus suggesting cellular adaptation.}, note = {Torres, Anaelle Dalzon, Bastien Collin-Faure, Veronique Diemer, Helene Fenel, Daphna Schoehn, Guy Cianferani, Sarah Carriere, Marie Rabilloud, Thierry eng PNREST 2015/032/Agence Nationale de Securite Sanitaire de l'Alimentation, de l'Environnement et du Travail ANR-16-CE34-0011; ANR-11-LABX-0064; ANR-10-INBS-05-02; ANR-17-EURE-0003; ANR-10-INBS-08-03/Agence Nationale de la Recherche Switzerland 2020/10/03 06:00 Nanomaterials (Basel). 2020 Sep 29;10(10). pii: nano10101939. doi: 10.3390/nano10101939.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Synthetic amorphous silica is one of the most used nanomaterials, and numerous toxicological studies have studied its effects. Most of these studies have used an acute exposure mode to investigate the effects immediately after exposure. However, this exposure modality does not allow the investigation of the persistence of the effects, which is a crucial aspect of silica toxicology, as exemplified by crystalline silica. In this paper, we extended the investigations by studying not only the responses immediately after exposure but also after a 72 h post-exposure recovery phase. We used a pyrolytic silica as the test nanomaterial, as this variant of synthetic amorphous silica has been shown to induce a more persistent inflammation in vivo than precipitated silica. To investigate macrophage responses to pyrolytic silica, we used a combination of proteomics and targeted experiments, which allowed us to show that most of the cellular functions that were altered immediately after exposure to pyrolytic silica at a subtoxic dose, such as energy metabolism and cell morphology, returned to normal at the end of the recovery period. However, some alterations, such as the inflammatory responses and some aldehyde detoxification proteins, were persistent. At the proteomic level, other alterations, such as proteins implicated in the endosomal/lysosomal pathway, were also persistent but resulted in normal function, thus suggesting cellular adaptation. |
Lesne, Jean; Locard-Paulet, Marie; Parra, Julien; ć, Dušan Zivkovi; Menneteau, Thomas; Bousquet, Marie-Pierre; Burlet-Schiltz, Odile; Marcoux, Julien Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks. Article de journal Nature communications, 11 (1), p. 6140, 2020. @article{Lesne2020, title = {Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks.}, author = {Jean Lesne and Marie Locard-Paulet and Julien Parra and Dušan Zivkovi{ć} and Thomas Menneteau and Marie-Pierre Bousquet and Odile Burlet-Schiltz and Julien Marcoux}, year = {2020}, date = {2020-01-01}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6140}, abstract = {Hydrogen-Deuterium eXchange coupled to Mass Spectrometry (HDX-MS) is now common practice in structural biology. However, it is most of the time applied to rather small oligomeric complexes. Here, we report on the use of HDX-MS to investigate conformational differences between the human standard 20S (std20S) and immuno 20S (i20s) proteasomes alone or in complex with PA28$alpha$$beta$ or PA28$gamma$ activators. Their solvent accessibility is analyzed through a dedicated bioinformatic pipeline including stringent statistical analysis and 3D visualization. These data confirm the existence of allosteric differences between the std20S and i20S at the surface of the $alpha$-ring triggered from inside the catalytic $beta$-ring. Additionally, binding of the PA28 regulators to the 20S proteasomes modify solvent accessibility due to conformational changes of the $beta$-rings. This work is not only a proof-of-concept that HDX-MS can be used to get structural insights on large multi-protein complexes in solution, it also demonstrates that the binding of the std20S or i20S subtype to any of its PA28 activator triggers allosteric changes that are specific to this 20S/PA28 pair.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Hydrogen-Deuterium eXchange coupled to Mass Spectrometry (HDX-MS) is now common practice in structural biology. However, it is most of the time applied to rather small oligomeric complexes. Here, we report on the use of HDX-MS to investigate conformational differences between the human standard 20S (std20S) and immuno 20S (i20s) proteasomes alone or in complex with PA28$alpha$$beta$ or PA28$gamma$ activators. Their solvent accessibility is analyzed through a dedicated bioinformatic pipeline including stringent statistical analysis and 3D visualization. These data confirm the existence of allosteric differences between the std20S and i20S at the surface of the $alpha$-ring triggered from inside the catalytic $beta$-ring. Additionally, binding of the PA28 regulators to the 20S proteasomes modify solvent accessibility due to conformational changes of the $beta$-rings. This work is not only a proof-of-concept that HDX-MS can be used to get structural insights on large multi-protein complexes in solution, it also demonstrates that the binding of the std20S or i20S subtype to any of its PA28 activator triggers allosteric changes that are specific to this 20S/PA28 pair. |
Sorroche, Fernando; Morales, Violette; ï, Sa; Pichereaux, Carole; Garnerone, Marie A; Zou, Lan; Soni, Badrish; Carpéné, Marie-Anne; Gargaros, Audrey; Maillet, Fabienne; Burlet-Schiltz, Odile; Poinsot, Verena; Polard, Patrice; Gough, Clare; Batut, Jacques The ex planta signal activity of a Medicago ribosomal uL2 protein suggests a moonlighting role in controlling secondary rhizobial infection. Article de journal PloS one, 15 (10), p. e0235446, 2020. @article{Sorroche2020, title = {The ex planta signal activity of a Medicago ribosomal uL2 protein suggests a moonlighting role in controlling secondary rhizobial infection.}, author = {Fernando Sorroche and Violette Morales and Sa{ï}da Mouffok and Carole Pichereaux and Marie A Garnerone and Lan Zou and Badrish Soni and Marie-Anne Carpéné and Audrey Gargaros and Fabienne Maillet and Odile Burlet-Schiltz and Verena Poinsot and Patrice Polard and Clare Gough and Jacques Batut}, year = {2020}, date = {2020-01-01}, journal = {PloS one}, volume = {15}, number = {10}, pages = {e0235446}, abstract = {We recently described a regulatory loop, which we termed autoregulation of infection (AOI), by which Sinorhizobium meliloti, a Medicago endosymbiont, downregulates the root susceptibility to secondary infection events via ethylene. AOI is initially triggered by so-far unidentified Medicago nodule signals named signal 1 and signal 1' whose transduction in bacteroids requires the S. meliloti outer-membrane-associated NsrA receptor protein and the cognate inner-membrane-associated adenylate cyclases, CyaK and CyaD1/D2, respectively. Here, we report on advances in signal 1 identification. Signal 1 activity is widespread as we robustly detected it in Medicago nodule extracts as well as in yeast and bacteria cell extracts. Biochemical analyses indicated a peptidic nature for signal 1 and, together with proteomic analyses, a universally conserved Medicago ribosomal protein of the uL2 family was identified as a candidate signal 1. Specifically, MtRPuL2A (MtrunA17Chr7g0247311) displays a strong signal activity that requires S. meliloti NsrA and CyaK, as endogenous signal 1. We have shown that MtRPuL2A is active in signaling only in a non-ribosomal form. A Medicago truncatula mutant in the major symbiotic transcriptional regulator MtNF-YA1 lacked most signal 1 activity, suggesting that signal 1 is under developmental control. Altogether, our results point to the MtRPuL2A ribosomal protein as the candidate for signal 1. Based on the Mtnf-ya1 mutant, we suggest a link between root infectiveness and nodule development. We discuss our findings in the context of ribosomal protein moonlighting.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We recently described a regulatory loop, which we termed autoregulation of infection (AOI), by which Sinorhizobium meliloti, a Medicago endosymbiont, downregulates the root susceptibility to secondary infection events via ethylene. AOI is initially triggered by so-far unidentified Medicago nodule signals named signal 1 and signal 1' whose transduction in bacteroids requires the S. meliloti outer-membrane-associated NsrA receptor protein and the cognate inner-membrane-associated adenylate cyclases, CyaK and CyaD1/D2, respectively. Here, we report on advances in signal 1 identification. Signal 1 activity is widespread as we robustly detected it in Medicago nodule extracts as well as in yeast and bacteria cell extracts. Biochemical analyses indicated a peptidic nature for signal 1 and, together with proteomic analyses, a universally conserved Medicago ribosomal protein of the uL2 family was identified as a candidate signal 1. Specifically, MtRPuL2A (MtrunA17Chr7g0247311) displays a strong signal activity that requires S. meliloti NsrA and CyaK, as endogenous signal 1. We have shown that MtRPuL2A is active in signaling only in a non-ribosomal form. A Medicago truncatula mutant in the major symbiotic transcriptional regulator MtNF-YA1 lacked most signal 1 activity, suggesting that signal 1 is under developmental control. Altogether, our results point to the MtRPuL2A ribosomal protein as the candidate for signal 1. Based on the Mtnf-ya1 mutant, we suggest a link between root infectiveness and nodule development. We discuss our findings in the context of ribosomal protein moonlighting. |
Le Moigne, Vincent ; Roux, Anne-Laure; Jobart-Malfait, Aude; Blanc, Landry; Chaoui, Karima; Burlet-Schiltz, Odile; Gaillard, Jean-Louis; Canaan, Stéphane; ô, Jér; Herrmann, Jean-Louis A TLR2-Activating Fraction From Mycobacterium abscessus Rough Variant Demonstrates Vaccine and Diagnostic Potential. Article de journal Frontiers in cellular and infection microbiology, 10 , p. 432, 2020. @article{LeMoigne2020, title = {A TLR2-Activating Fraction From Mycobacterium abscessus Rough Variant Demonstrates Vaccine and Diagnostic Potential.}, author = {Vincent {Le Moigne} and Anne-Laure Roux and Aude Jobart-Malfait and Landry Blanc and Karima Chaoui and Odile Burlet-Schiltz and Jean-Louis Gaillard and Stéphane Canaan and Jér{ô}me Nigou and Jean-Louis Herrmann}, year = {2020}, date = {2020-01-01}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, pages = {432}, abstract = {Mycobacterium abscessus is a prevalent pathogenic mycobacterium in cystic fibrosis (CF) patients and one of the most highly drug resistant mycobacterial species to antimicrobial agents. It possesses the property to transition from a smooth (S) to a rough (R) morphotype, thereby influencing the host innate immune response. This transition from the S to the R morphotype takes place in patients with an exacerbation of the disease and a persistence of M. abscessus. We have previously shown that the exacerbation of the Toll-like receptor 2 (TLR2)-mediated inflammatory response, following this S to R transition, is essentially due to overproduction of bacilli cell envelope surface compounds, which we were able to extract by mechanical treatment and isolation by solvent partition in a fraction called interphase. Here, we set up a purification procedure guided by bioactivity to isolate a fraction from the R variant of M. abscessus cells which exhibits a high TLR2 stimulating activity, referred to as TLR2-enriched fraction (TLR2eF). As expected, TLR2eF was found to contain several lipoproteins and proteins known to be stimuli for TLR2. Vaccination with TLR2eF showed no protection toward an M. abscessus aerosol challenge, but provided mild protection in $Delta$F508 mice and their FVB littermates when intravenously challenged by M. abscessus. Interestingly however, antibodies against TLR2eF compounds were detected during disease in CF patients. In conclusion, we show the potential for compounds in TLR2eF as vaccine and diagnostic candidates, in order to enhance diagnosis, prevent and/or treat M. abscessus-related infections.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mycobacterium abscessus is a prevalent pathogenic mycobacterium in cystic fibrosis (CF) patients and one of the most highly drug resistant mycobacterial species to antimicrobial agents. It possesses the property to transition from a smooth (S) to a rough (R) morphotype, thereby influencing the host innate immune response. This transition from the S to the R morphotype takes place in patients with an exacerbation of the disease and a persistence of M. abscessus. We have previously shown that the exacerbation of the Toll-like receptor 2 (TLR2)-mediated inflammatory response, following this S to R transition, is essentially due to overproduction of bacilli cell envelope surface compounds, which we were able to extract by mechanical treatment and isolation by solvent partition in a fraction called interphase. Here, we set up a purification procedure guided by bioactivity to isolate a fraction from the R variant of M. abscessus cells which exhibits a high TLR2 stimulating activity, referred to as TLR2-enriched fraction (TLR2eF). As expected, TLR2eF was found to contain several lipoproteins and proteins known to be stimuli for TLR2. Vaccination with TLR2eF showed no protection toward an M. abscessus aerosol challenge, but provided mild protection in $Delta$F508 mice and their FVB littermates when intravenously challenged by M. abscessus. Interestingly however, antibodies against TLR2eF compounds were detected during disease in CF patients. In conclusion, we show the potential for compounds in TLR2eF as vaccine and diagnostic candidates, in order to enhance diagnosis, prevent and/or treat M. abscessus-related infections. |
Locard-Paulet, Marie; Voisinne, Guillaume; Froment, Carine; Goncalves Menoita, Marisa ; Ounoughene, Youcef; Girard, Laura; Gregoire, Claude; Mori, Daiki; Martinez, Manuel; Luche, Hervé; ô, Jer; Malissen, Marie; Burlet-Schiltz, Odile; Malissen, Bernard; de Peredo, Anne; Roncagalli, Romain LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions. Article de journal Molecular systems biology, 16 (7), p. e9524, 2020. @article{Locard-Paulet2020, title = {LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions.}, author = {Marie Locard-Paulet and Guillaume Voisinne and Carine Froment and Marisa {Goncalves Menoita} and Youcef Ounoughene and Laura Girard and Claude Gregoire and Daiki Mori and Manuel Martinez and Hervé Luche and Jer{ô}me Garin and Marie Malissen and Odile Burlet-Schiltz and Bernard Malissen and Anne de Peredo and Romain Roncagalli}, year = {2020}, date = {2020-01-01}, journal = {Molecular systems biology}, volume = {16}, number = {7}, pages = {e9524}, abstract = {T-cell receptor (TCR) ligation-mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time-resolved high-resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min after TCR stimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T-cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that the ITSN2 adaptor protein regulated T-cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T-cell activation. LymphoAtlas is accessible to the community at: https://bmm-lab.github.io/LymphoAtlas.}, keywords = {}, pubstate = {published}, tppubtype = {article} } T-cell receptor (TCR) ligation-mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time-resolved high-resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min after TCR stimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T-cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that the ITSN2 adaptor protein regulated T-cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T-cell activation. LymphoAtlas is accessible to the community at: https://bmm-lab.github.io/LymphoAtlas. |
Thouvenel, Laurie; Prevot, Gautier; Chiaradia, Laura; Parra, Julien; Mouton-Barbosa, Emmanuelle; Locard-Paulet, Marie; Marcoux, Julien; Tropis, Maryelle; Burlet-Schiltz, Odile; Daffé, Mamadou; Guilhot, Christophe; Etienne, Gilles; Chalut, Christian The final assembly of trehalose polyphleates takes place within the outer layer of the mycobacterial cell envelope. Article de journal The Journal of biological chemistry, 295 (32), p. 11184–11194, 2020. @article{Thouvenel2020, title = {The final assembly of trehalose polyphleates takes place within the outer layer of the mycobacterial cell envelope.}, author = {Laurie Thouvenel and Gautier Prevot and Laura Chiaradia and Julien Parra and Emmanuelle Mouton-Barbosa and Marie Locard-Paulet and Julien Marcoux and Maryelle Tropis and Odile Burlet-Schiltz and Mamadou Daffé and Christophe Guilhot and Gilles Etienne and Christian Chalut}, year = {2020}, date = {2020-01-01}, journal = {The Journal of biological chemistry}, volume = {295}, number = {32}, pages = {11184--11194}, abstract = {Trehalose polyphleates (TPP) are high-molecular-weight, surface-exposed glycolipids present in a broad range of nontuberculous mycobacteria. These compounds consist of a trehalose core bearing polyunsaturated fatty acyl substituents (called phleic acids) and a straight-chain fatty acid residue and share a common basic structure with trehalose-based glycolipids produced by Mycobacterium tuberculosis TPP production starts in the cytosol with the formation of a diacyltrehalose intermediate. An acyltransferase, called PE, subsequently catalyzes the transfer of phleic acids onto diacyltrehalose to form TPP, and an MmpL transporter promotes the export of TPP or its precursor across the plasma membrane. PE is predicted to be an anchored membrane protein, but its topological organization is unknown, raising questions about the subcellular localization of the final stage of TPP biosynthesis and the chemical nature of the substrates that are translocated by the MmpL transporter. Here, using genetic, biochemical, and proteomic approaches, we established that PE of Mycobacterium smegmatis is exported to the cell envelope following cleavage of its signal peptide and that this process is required for TPP biosynthesis, indicating that the last step of TPP formation occurs in the outer layers of the mycobacterial cell envelope. These results provide detailed insights into the molecular mechanisms controlling TPP formation and transport to the cell surface, enabling us to propose an updated model of the TPP biosynthetic pathway. Because the molecular mechanisms of glycolipid production are conserved among mycobacteria, these findings obtained with PE from M. smegmatis may offer clues to glycolipid formation in M. tuberculosis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Trehalose polyphleates (TPP) are high-molecular-weight, surface-exposed glycolipids present in a broad range of nontuberculous mycobacteria. These compounds consist of a trehalose core bearing polyunsaturated fatty acyl substituents (called phleic acids) and a straight-chain fatty acid residue and share a common basic structure with trehalose-based glycolipids produced by Mycobacterium tuberculosis TPP production starts in the cytosol with the formation of a diacyltrehalose intermediate. An acyltransferase, called PE, subsequently catalyzes the transfer of phleic acids onto diacyltrehalose to form TPP, and an MmpL transporter promotes the export of TPP or its precursor across the plasma membrane. PE is predicted to be an anchored membrane protein, but its topological organization is unknown, raising questions about the subcellular localization of the final stage of TPP biosynthesis and the chemical nature of the substrates that are translocated by the MmpL transporter. Here, using genetic, biochemical, and proteomic approaches, we established that PE of Mycobacterium smegmatis is exported to the cell envelope following cleavage of its signal peptide and that this process is required for TPP biosynthesis, indicating that the last step of TPP formation occurs in the outer layers of the mycobacterial cell envelope. These results provide detailed insights into the molecular mechanisms controlling TPP formation and transport to the cell surface, enabling us to propose an updated model of the TPP biosynthetic pathway. Because the molecular mechanisms of glycolipid production are conserved among mycobacteria, these findings obtained with PE from M. smegmatis may offer clues to glycolipid formation in M. tuberculosis. |
Le, Nguyen-Hung; Locard-Paulet, Marie; Stella, Alexandre; Tomas, Nicolas; Molle, Virginie; Burlet-Schiltz, Odile; Daffé, Mamadou; Marrakchi, Hedia The protein kinase PknB negatively regulates biosynthesis and trafficking of mycolic acids in mycobacteria. Article de journal Journal of lipid research, 61 (8), p. 1180–1191, 2020. @article{Le2020, title = {The protein kinase PknB negatively regulates biosynthesis and trafficking of mycolic acids in mycobacteria.}, author = {Nguyen-Hung Le and Marie Locard-Paulet and Alexandre Stella and Nicolas Tomas and Virginie Molle and Odile Burlet-Schiltz and Mamadou Daffé and Hedia Marrakchi}, year = {2020}, date = {2020-01-01}, journal = {Journal of lipid research}, volume = {61}, number = {8}, pages = {1180--1191}, abstract = {Mycobacterium tuberculosis is the causative agent of tuberculosis and remains one of the most widespread and deadliest bacterial pathogens in the world. A distinguishing feature of mycobacteria that sets them apart from other bacteria is the unique architecture of their cell wall, characterized by various species-specific lipids, most notably mycolic acids (MAs). Therefore, targeted inhibition of enzymes involved in MA biosynthesis, transport, and assembly has been extensively explored in drug discovery. Additionally, more recent evidence suggests that many enzymes in the MA biosynthesis pathway are regulated by kinase-mediated phosphorylation, thus opening additional drug-development opportunities. However, how phosphorylation regulates MA production remains unclear. Here, we used genetic strategies combined with lipidomics and phosphoproteomics approaches to investigate the role of protein phosphorylation in Mycobacterium The results of this analysis revealed that the Ser/Thr protein kinase PknB regulates the export of MAs and promotes the remodeling of the mycobacterial cell envelope. In particular, we identified the essential MmpL3 as a substrate negatively regulated by PknB. Taken together, our findings add to the understanding of how PknB activity affects the mycobacterial MA biosynthesis pathway and reveal the essential role of protein phosphorylation/dephosphorylation in governing lipid metabolism, paving the way for novel antimycobacterial strategies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mycobacterium tuberculosis is the causative agent of tuberculosis and remains one of the most widespread and deadliest bacterial pathogens in the world. A distinguishing feature of mycobacteria that sets them apart from other bacteria is the unique architecture of their cell wall, characterized by various species-specific lipids, most notably mycolic acids (MAs). Therefore, targeted inhibition of enzymes involved in MA biosynthesis, transport, and assembly has been extensively explored in drug discovery. Additionally, more recent evidence suggests that many enzymes in the MA biosynthesis pathway are regulated by kinase-mediated phosphorylation, thus opening additional drug-development opportunities. However, how phosphorylation regulates MA production remains unclear. Here, we used genetic strategies combined with lipidomics and phosphoproteomics approaches to investigate the role of protein phosphorylation in Mycobacterium The results of this analysis revealed that the Ser/Thr protein kinase PknB regulates the export of MAs and promotes the remodeling of the mycobacterial cell envelope. In particular, we identified the essential MmpL3 as a substrate negatively regulated by PknB. Taken together, our findings add to the understanding of how PknB activity affects the mycobacterial MA biosynthesis pathway and reveal the essential role of protein phosphorylation/dephosphorylation in governing lipid metabolism, paving the way for novel antimycobacterial strategies. |
Soler, Laura; Stella, Alexandre; Seva, Juan; Pallarés, Francisco Jose; Lahjouji, Tarek; Burlet-Schiltz, Odile; Oswald, Isabelle P Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine. Article de journal Journal of proteomics, 224 , p. 103842, 2020. @article{Soler2020, title = {Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine.}, author = {Laura Soler and Alexandre Stella and Juan Seva and Francisco Jose Pallarés and Tarek Lahjouji and Odile Burlet-Schiltz and Isabelle P Oswald}, year = {2020}, date = {2020-01-01}, journal = {Journal of proteomics}, volume = {224}, pages = {103842}, address = {Netherlands}, abstract = {Intestinal epithelial homeostasis is regulated by a complex network of signaling pathways. Among them is estrogen signaling, important for the proliferation and differentiation of epithelial cells, immune signaling and metabolism. The mycotoxin zearalenone (ZEN) is an estrogen disruptor naturally found in food and feed. The exposure of the intestine to ZEN has toxic effects including alteration of the immune status and is possibly implicated in carcinogenesis, but the molecular mechanisms linked with these effects are not clear. Our objective was to explore the proteome changes induced by a short, non-cytotoxic exposure to ZEN in the intestine using pig jejunal explants. Our results indicated that ZEN promotes little proteome changes, but significantly related with an induction of ER$alpha$ signaling and a consequent disruption of highly interrelated signaling cascades, such as NF-$kappa$B, ERK1/2, CDX2 and HIF1$alpha$. The toxicity of ZEN leads also to an altered immune status characterized by the activation of the chemokine CXCR4/SDF-1 axis and an accumulation of MHC-I proteins. Our results connect the estrogen disrupting activity of ZEN with its intestinal toxic effect, associating the exposure to ZEN with cell-signaling disorders similar to those involved in the onset and progression of diseases such as cancer and chronic inflammatory disorders. SIGNIFICANCE: The proteomics results presented in our study indicate that the endocrine disruptor activity of ZEN is able to regulate a cascade of highly inter-connected signaling events essential for the small intestinal crypt-villus cycle and immune status. These molecular mechanisms are also implicated in the onset and progress of intestinal immune disorders and cancer indicating that exposure to ZEN could play an important role in intestinal pathogenesis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Intestinal epithelial homeostasis is regulated by a complex network of signaling pathways. Among them is estrogen signaling, important for the proliferation and differentiation of epithelial cells, immune signaling and metabolism. The mycotoxin zearalenone (ZEN) is an estrogen disruptor naturally found in food and feed. The exposure of the intestine to ZEN has toxic effects including alteration of the immune status and is possibly implicated in carcinogenesis, but the molecular mechanisms linked with these effects are not clear. Our objective was to explore the proteome changes induced by a short, non-cytotoxic exposure to ZEN in the intestine using pig jejunal explants. Our results indicated that ZEN promotes little proteome changes, but significantly related with an induction of ER$alpha$ signaling and a consequent disruption of highly interrelated signaling cascades, such as NF-$kappa$B, ERK1/2, CDX2 and HIF1$alpha$. The toxicity of ZEN leads also to an altered immune status characterized by the activation of the chemokine CXCR4/SDF-1 axis and an accumulation of MHC-I proteins. Our results connect the estrogen disrupting activity of ZEN with its intestinal toxic effect, associating the exposure to ZEN with cell-signaling disorders similar to those involved in the onset and progression of diseases such as cancer and chronic inflammatory disorders. SIGNIFICANCE: The proteomics results presented in our study indicate that the endocrine disruptor activity of ZEN is able to regulate a cascade of highly inter-connected signaling events essential for the small intestinal crypt-villus cycle and immune status. These molecular mechanisms are also implicated in the onset and progress of intestinal immune disorders and cancer indicating that exposure to ZEN could play an important role in intestinal pathogenesis. |
ë, Ga; è, Hél; Aloulou, Meryem; Rouquié, Nelly; Yang, Cui; è, Marl; è, Myl; Benamar, Mehdi; Ducatez, Mariette; Song, Ki-Duk; Burlet-Schiltz, Odile; Saoudi, Abdelhadi; Love, Paul E; Fazilleau, Nicolas; de Peredo, Anne; Lesourne, Renaud CD5 signalosome coordinates antagonist TCR signals to control the generation of Treg cells induced by foreign antigens. Article de journal Proceedings of the National Academy of Sciences of the United States of America, 117 (23), p. 12969–12979, 2020. @article{Blaize2020, title = {CD5 signalosome coordinates antagonist TCR signals to control the generation of Treg cells induced by foreign antigens.}, author = {Ga{ë}tan Blaize and Hél{è}ne Daniels-Treffandier and Meryem Aloulou and Nelly Rouquié and Cui Yang and Marl{è}ne Marcellin and Myl{è}ne Gador and Mehdi Benamar and Mariette Ducatez and Ki-Duk Song and Odile Burlet-Schiltz and Abdelhadi Saoudi and Paul E Love and Nicolas Fazilleau and Anne de Peredo and Renaud Lesourne}, year = {2020}, date = {2020-01-01}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {23}, pages = {12969--12979}, abstract = {CD5 is characterized as an inhibitory coreceptor with an important regulatory role during T cell development. The molecular mechanism by which CD5 operates has been puzzling and its function in mature T cells suggests promoting rather than repressing effects on immune responses. Here, we combined quantitative mass spectrometry and genetic studies to analyze the components and the activity of the CD5 signaling machinery in primary T cells. We found that T cell receptor (TCR) engagement induces the selective phosphorylation of CD5 tyrosine 429, which serves as a docking site for proteins with adaptor functions (c-Cbl, CIN85, CRKL), connecting CD5 to positive (PI3K) and negative (UBASH3A, SHIP1) regulators of TCR signaling. c-CBL acts as a coordinator in this complex enabling CD5 to synchronize positive and negative feedbacks on TCR signaling through the other components. Disruption of CD5 signalosome in mutant mice reveals that it modulates TCR signal outputs to selectively repress the transactivation of Foxp3 and limit the inopportune induction of peripherally induced regulatory T cells during immune responses against foreign antigen. Our findings bring insights into the paradigm of coreceptor signaling, suggesting that, in addition to providing dualistic enhancing or dampening inputs, coreceptors can engage concomitant stimulatory and inhibitory signaling events, which act together to promote specific functional outcomes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } CD5 is characterized as an inhibitory coreceptor with an important regulatory role during T cell development. The molecular mechanism by which CD5 operates has been puzzling and its function in mature T cells suggests promoting rather than repressing effects on immune responses. Here, we combined quantitative mass spectrometry and genetic studies to analyze the components and the activity of the CD5 signaling machinery in primary T cells. We found that T cell receptor (TCR) engagement induces the selective phosphorylation of CD5 tyrosine 429, which serves as a docking site for proteins with adaptor functions (c-Cbl, CIN85, CRKL), connecting CD5 to positive (PI3K) and negative (UBASH3A, SHIP1) regulators of TCR signaling. c-CBL acts as a coordinator in this complex enabling CD5 to synchronize positive and negative feedbacks on TCR signaling through the other components. Disruption of CD5 signalosome in mutant mice reveals that it modulates TCR signal outputs to selectively repress the transactivation of Foxp3 and limit the inopportune induction of peripherally induced regulatory T cells during immune responses against foreign antigen. Our findings bring insights into the paradigm of coreceptor signaling, suggesting that, in addition to providing dualistic enhancing or dampening inputs, coreceptors can engage concomitant stimulatory and inhibitory signaling events, which act together to promote specific functional outcomes. |
Bouyssié, David; Hesse, Anne-Marie; Mouton-Barbosa, Emmanuelle; Rompais, Magali; Macron, Charlotte; Carapito, Christine; de Peredo, Anne; Couté, Yohann; Dupierris, Véronique; Burel, Alexandre; Menetrey, Jean-Philippe; Kalaitzakis, Andrea; Poisat, Julie; Romdhani, Aymen; Burlet-Schiltz, Odile; Cianférani, Sarah; Garin, Jerome; Bruley, Christophe Proline: an efficient and user-friendly software suite for large-scale proteomics. Article de journal Bioinformatics (Oxford, England), 36 (10), p. 3148–3155, 2020. @article{Bouyssie2020, title = {Proline: an efficient and user-friendly software suite for large-scale proteomics.}, author = {David Bouyssié and Anne-Marie Hesse and Emmanuelle Mouton-Barbosa and Magali Rompais and Charlotte Macron and Christine Carapito and Anne de Peredo and Yohann Couté and Véronique Dupierris and Alexandre Burel and Jean-Philippe Menetrey and Andrea Kalaitzakis and Julie Poisat and Aymen Romdhani and Odile Burlet-Schiltz and Sarah Cianférani and Jerome Garin and Christophe Bruley}, year = {2020}, date = {2020-01-01}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {10}, pages = {3148--3155}, abstract = {MOTIVATION: The proteomics field requires the production and publication of reliable mass spectrometry-based identification and quantification results. Although many tools or algorithms exist, very few consider the importance of combining, in a unique software environment, efficient processing algorithms and a data management system to process and curate hundreds of datasets associated with a single proteomics study. RESULTS: Here, we present Proline, a robust software suite for analysis of MS-based proteomics data, which collects, processes and allows visualization and publication of proteomics datasets. We illustrate its ease of use for various steps in the validation and quantification workflow, its data curation capabilities and its computational efficiency. The DDA label-free quantification workflow efficiency was assessed by comparing results obtained with Proline to those obtained with a widely used software using a spiked-in sample. This assessment demonstrated Proline's ability to provide high quantification accuracy in a user-friendly interface for datasets of any size. AVAILABILITY AND IMPLEMENTATION: Proline is available for Windows and Linux under CECILL open-source license. It can be deployed in client-server mode or in standalone mode at http://proline.profiproteomics.fr/#downloads. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, keywords = {}, pubstate = {published}, tppubtype = {article} } MOTIVATION: The proteomics field requires the production and publication of reliable mass spectrometry-based identification and quantification results. Although many tools or algorithms exist, very few consider the importance of combining, in a unique software environment, efficient processing algorithms and a data management system to process and curate hundreds of datasets associated with a single proteomics study. RESULTS: Here, we present Proline, a robust software suite for analysis of MS-based proteomics data, which collects, processes and allows visualization and publication of proteomics datasets. We illustrate its ease of use for various steps in the validation and quantification workflow, its data curation capabilities and its computational efficiency. The DDA label-free quantification workflow efficiency was assessed by comparing results obtained with Proline to those obtained with a widely used software using a spiked-in sample. This assessment demonstrated Proline's ability to provide high quantification accuracy in a user-friendly interface for datasets of any size. AVAILABILITY AND IMPLEMENTATION: Proline is available for Windows and Linux under CECILL open-source license. It can be deployed in client-server mode or in standalone mode at http://proline.profiproteomics.fr/#downloads. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. |
Pechalrieu, Dany; Assemat, Fanny; Halby, Ludovic; Marcellin, Marlene; Yan, Pengrong; Chaoui, Karima; Sharma, Sahil; Chiosis, Gabriela; Burlet-Schiltz, Odile; Arimondo, Paola B; Lopez, Marie Bisubstrate-Type Chemical Probes Identify GRP94 as a Potential Target of Cytosine-Containing Adenosine Analogs. Article de journal ACS chemical biology, 15 (4), p. 952–961, 2020. @article{Pechalrieu2020, title = {Bisubstrate-Type Chemical Probes Identify GRP94 as a Potential Target of Cytosine-Containing Adenosine Analogs.}, author = {Dany Pechalrieu and Fanny Assemat and Ludovic Halby and Marlene Marcellin and Pengrong Yan and Karima Chaoui and Sahil Sharma and Gabriela Chiosis and Odile Burlet-Schiltz and Paola B Arimondo and Marie Lopez}, year = {2020}, date = {2020-01-01}, journal = {ACS chemical biology}, volume = {15}, number = {4}, pages = {952--961}, abstract = {We synthesized affinity-based chemical probes of cytosine-adenosine bisubstrate analogs and identified several potential targets by proteomic analysis. The validation of the proteomic analysis identified the chemical probe as a specific inhibitor of glucose-regulated protein 94 (GRP94), a potential drug target for several types of cancers. Therefore, as a result of the use of bisubstrate-type chemical probes and a chemical-biology methodology, this work opens the way to the development of a new family of GRP94 inhibitors that could potentially be of therapeutic interest.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We synthesized affinity-based chemical probes of cytosine-adenosine bisubstrate analogs and identified several potential targets by proteomic analysis. The validation of the proteomic analysis identified the chemical probe as a specific inhibitor of glucose-regulated protein 94 (GRP94), a potential drug target for several types of cancers. Therefore, as a result of the use of bisubstrate-type chemical probes and a chemical-biology methodology, this work opens the way to the development of a new family of GRP94 inhibitors that could potentially be of therapeutic interest. |
Imbert, Caroline; Montfort, Anne; Fraisse, Marine; Marcheteau, Elie; Gilhodes, Julia; Martin, Elodie; Bertrand, Florie; è, Marl; Burlet-Schiltz, Odile; de Peredo, Anne Gonzalez; Garcia, Virginie; Carpentier, Stéphane; Tartare-Deckert, Sophie; Brousset, Pierre; Rochaix, Philippe; Puisset, Florent; Filleron, Thomas; Meyer, Nicolas; Lamant, Laurence; Levade, Thierry; Ségui, Bruno; Andrieu-Abadie, Nathalie; Colacios, Céline Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1. Article de journal Nature communications, 11 (1), p. 437, 2020. @article{Imbert2020, title = {Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1.}, author = {Caroline Imbert and Anne Montfort and Marine Fraisse and Elie Marcheteau and Julia Gilhodes and Elodie Martin and Florie Bertrand and Marl{è}ne Marcellin and Odile Burlet-Schiltz and Anne Gonzalez de Peredo and Virginie Garcia and Stéphane Carpentier and Sophie Tartare-Deckert and Pierre Brousset and Philippe Rochaix and Florent Puisset and Thomas Filleron and Nicolas Meyer and Laurence Lamant and Thierry Levade and Bruno Ségui and Nathalie Andrieu-Abadie and Céline Colacios}, year = {2020}, date = {2020-01-01}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {437}, abstract = {Immune checkpoint inhibitors (ICIs) have dramatically modified the prognosis of several advanced cancers, however many patients still do not respond to treatment. Optimal results might be obtained by targeting cancer cell metabolism to modulate the immunosuppressive tumor microenvironment. Here, we identify sphingosine kinase-1 (SK1) as a key regulator of anti-tumor immunity. Increased expression of SK1 in tumor cells is significantly associated with shorter survival in metastatic melanoma patients treated with anti-PD-1. Targeting SK1 markedly enhances the responses to ICI in murine models of melanoma, breast and colon cancer. Mechanistically, SK1 silencing decreases the expression of various immunosuppressive factors in the tumor microenvironment to limit regulatory T cell (Treg) infiltration. Accordingly, a SK1-dependent immunosuppressive signature is also observed in human melanoma biopsies. Altogether, this study identifies SK1 as a checkpoint lipid kinase that could be targeted to enhance immunotherapy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Immune checkpoint inhibitors (ICIs) have dramatically modified the prognosis of several advanced cancers, however many patients still do not respond to treatment. Optimal results might be obtained by targeting cancer cell metabolism to modulate the immunosuppressive tumor microenvironment. Here, we identify sphingosine kinase-1 (SK1) as a key regulator of anti-tumor immunity. Increased expression of SK1 in tumor cells is significantly associated with shorter survival in metastatic melanoma patients treated with anti-PD-1. Targeting SK1 markedly enhances the responses to ICI in murine models of melanoma, breast and colon cancer. Mechanistically, SK1 silencing decreases the expression of various immunosuppressive factors in the tumor microenvironment to limit regulatory T cell (Treg) infiltration. Accordingly, a SK1-dependent immunosuppressive signature is also observed in human melanoma biopsies. Altogether, this study identifies SK1 as a checkpoint lipid kinase that could be targeted to enhance immunotherapy. |
Clement, Emily; Lazar, Ikrame; Attané, Camille; Carrié, Lorry; Dauvillier, Stéphanie; Ducoux-Petit, Manuelle; Esteve, David; Menneteau, Thomas; Moutahir, Mohamed; Le Gonidec, Sophie ; Dalle, Stéphane; Valet, Philippe; Burlet-Schiltz, Odile; Muller, Catherine; Nieto, Laurence Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. Article de journal The EMBO journal, 39 (3), p. e102525, 2020. @article{Clement2020, title = {Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells.}, author = {Emily Clement and Ikrame Lazar and Camille Attané and Lorry Carrié and Stéphanie Dauvillier and Manuelle Ducoux-Petit and David Esteve and Thomas Menneteau and Mohamed Moutahir and Sophie {Le Gonidec} and Stéphane Dalle and Philippe Valet and Odile Burlet-Schiltz and Catherine Muller and Laurence Nieto}, year = {2020}, date = {2020-01-01}, journal = {The EMBO journal}, volume = {39}, number = {3}, pages = {e102525}, abstract = {Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity. |
Pirro, Martina; Rombouts, Yoann; Stella, Alexandre; Neyrolles, Olivier; Burlet-Schiltz, Odile; van Vliet, Sandra J; de Ru, Arnoud H; Mohammed, Yassene; Wuhrer, Manfred; van Veelen, Peter A; Hensbergen, Paul J Characterization of Macrophage Galactose-type Lectin (MGL) ligands in colorectal cancer cell lines. Article de journal Biochimica et biophysica acta. General subjects, 1864 (4), p. 129513, 2020. @article{Pirro2020, title = {Characterization of Macrophage Galactose-type Lectin (MGL) ligands in colorectal cancer cell lines.}, author = {Martina Pirro and Yoann Rombouts and Alexandre Stella and Olivier Neyrolles and Odile Burlet-Schiltz and Sandra J van Vliet and Arnoud H de Ru and Yassene Mohammed and Manfred Wuhrer and Peter A van Veelen and Paul J Hensbergen}, year = {2020}, date = {2020-01-01}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1864}, number = {4}, pages = {129513}, address = {Netherlands}, abstract = {BACKGROUND: The Ca(2+)-dependent C-type lectin receptor Macrophage Galactose-type Lectin (MGL) is highly expressed by tolerogenic dendritic cells (DC) and macrophages. MGL exhibits a high binding specificity for terminal alpha- and beta-linked GalNAc residues found in Tn, sTn and LacdiNAc antigens. These glycan epitopes are often overexpressed in colorectal cancer (CRC), and, as such, MGL can be used to discriminate tumor from the corresponding healthy tissues. Moreover, the high expression of MGL ligands is associated with poor disease-free survival in stage III of CRC tumors. Nonetheless, the glycoproteins expressed by tumor cells that are recognized by MGL have hitherto remained elusive. METHODS: Using a panel of three CRC cell lines (HCT116, HT29 and LS174T), recapitulating CRC diversity, we performed FACS staining and pull-down assays using a recombinant soluble form of MGL (and a mutant MGL as control) combined with mass spectrometry-based (glyco)proteomics. RESULTS: HCT116 and HT29, but not LS174T, are high MGL-binding CRC cell lines. On these cells, the major cell surface binding proteins are receptors (e.g. MET, PTK7, SORL1, PTPRF) and integrins (ITGB1, ITGA3). From these proteins, several N- and/or O-glycopeptides were identified, of which some carried either a LacdiNAc or Tn epitope. CONCLUSIONS: We have identified cell surface MGL-ligands on CRC cell lines. GENERAL SIGNIFICANCE: Advances in (glyco)proteomics have led to identification of candidate key mediators of immune-evasion and tumor growth in CRC.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The Ca(2+)-dependent C-type lectin receptor Macrophage Galactose-type Lectin (MGL) is highly expressed by tolerogenic dendritic cells (DC) and macrophages. MGL exhibits a high binding specificity for terminal alpha- and beta-linked GalNAc residues found in Tn, sTn and LacdiNAc antigens. These glycan epitopes are often overexpressed in colorectal cancer (CRC), and, as such, MGL can be used to discriminate tumor from the corresponding healthy tissues. Moreover, the high expression of MGL ligands is associated with poor disease-free survival in stage III of CRC tumors. Nonetheless, the glycoproteins expressed by tumor cells that are recognized by MGL have hitherto remained elusive. METHODS: Using a panel of three CRC cell lines (HCT116, HT29 and LS174T), recapitulating CRC diversity, we performed FACS staining and pull-down assays using a recombinant soluble form of MGL (and a mutant MGL as control) combined with mass spectrometry-based (glyco)proteomics. RESULTS: HCT116 and HT29, but not LS174T, are high MGL-binding CRC cell lines. On these cells, the major cell surface binding proteins are receptors (e.g. MET, PTK7, SORL1, PTPRF) and integrins (ITGB1, ITGA3). From these proteins, several N- and/or O-glycopeptides were identified, of which some carried either a LacdiNAc or Tn epitope. CONCLUSIONS: We have identified cell surface MGL-ligands on CRC cell lines. GENERAL SIGNIFICANCE: Advances in (glyco)proteomics have led to identification of candidate key mediators of immune-evasion and tumor growth in CRC. |
2019 |
Bouyssié, D; Lesne, J; Locard-Paulet, M; Albigot, R; Burlet-Schiltz, O; Marcoux, J HDX-Viewer: interactive 3D visualization of hydrogen-deuterium exchange data Article de journal Bioinformatics, 35 (24), p. 5331–5333, 2019. @article{pmid31287496, title = {HDX-Viewer: interactive 3D visualization of hydrogen-deuterium exchange data}, author = {D Bouyssié and J Lesne and M Locard-Paulet and R Albigot and O Burlet-Schiltz and J Marcoux}, doi = {10.1093/bioinformatics/btz550}, year = {2019}, date = {2019-12-15}, journal = {Bioinformatics}, volume = {35}, number = {24}, pages = {5331--5333}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Santin, Y; Fazal, L; Sainte-Marie, Y; Sicard, P; Maggiorani, D; Tortosa, F; Y?cel, Y Y; Teyssedre, L; Rouquette, J; Marcellin, M; Vindis, C; Shih, J C; Lairez, O; Burlet-Schiltz, O; Parini, A; Lezoualc'h, F; Mialet-Perez, J Mitochondrial 4-ĦNE derived from MAO-A promotes mitoCa2+ overload in chronic postischemic cardiac remodeling Article de journal Cell Death Differ., 2019. @article{pmid31819159, title = {Mitochondrial 4-ĦNE derived from MAO-A promotes mitoCa2+ overload in chronic postischemic cardiac remodeling}, author = {Y Santin and L Fazal and Y Sainte-Marie and P Sicard and D Maggiorani and F Tortosa and Y Y Y?cel and L Teyssedre and J Rouquette and M Marcellin and C Vindis and J C Shih and O Lairez and O Burlet-Schiltz and A Parini and F Lezoualc'h and J Mialet-Perez}, doi = {10.1038/s41418-019-0470-y}, year = {2019}, date = {2019-12-09}, journal = {Cell Death Differ.}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
