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Publications Départements Biologie Cellulaire


  • T. Avin-Wittenberg, F. Baluška, P. V. Bozhkov, P. H. Elander, A. R. Fernie, G. Galili, A. Hassan, D. Hofius, E. Isono, R. Le Bars, C. Masclaux-Daubresse, E. A. Minina, H. Peled-Zehavi, N. S. Coll, L. M. Sandalio, B. Satiat-Jeunemaitre, A. Sirko, P. S. Testillano, et H. Batoko, « Autophagy-related approaches for improving nutrient use efficiency and crop yield protection », Journal of Experimental Botany, vol. 69, nᵒ 6, p. 1335-1353, mars 2018.
    Mots-clés : BIOCELL, CYTO, DYNBSJ, PF, PHOT.

  • T. Avin-Wittenberg, F. Baluška, P. V. Bozhkov, P. H. Elander, A. R. Fernie, G. Galili, A. Hassan, D. Hofius, E. Isono, R. Le Bars, C. Masclaux-Daubresse, E. A. Minina, H. Peled-Zehavi, N. S. Coll, L. M. Sandalio, B. Satiat-Jeunemaitre, A. Sirko, P. S. Testillano, et H. Batoko, « Corrigendum: Autophagy-related approaches for improving nutrient use efficiency and crop yield protection », Journal of Experimental Botany, vol. 69, nᵒ 12, p. 3173, mai 2018.
    Mots-clés : BIOCELL, CYTO, DYNBSJ, PF, PHOT.

  • E. L. Bastow, V. S. Garcia de la Torre, A. E. Maclean, R. T. Green, S. Merlot, S. Thomine, et J. Balk, « Vacuolar iron stores gated by NRAMP3 and NRAMP4 are the primary source of iron in germinating seeds », Plant Physiology, vol. 177, nᵒ 3, p. 1267-1276, mai 2018.
    Résumé : During seed germination, iron (Fe) stored in vacuoles is exported by the redundant NRAMP3 and NRAMP4 transporter proteins. A double nramp3 nramp4 mutant is unable to mobilize Fe stores and does not develop in the absence of external Fe. We used RNA sequencing to compare gene expression in nramp3 nramp4 and wild type during germination and early seedling development. Even though sufficient Fe was supplied, the Fe-responsive transcription factors bHLH38, 39, 100 and 101 and their downstream targets FRO2 and IRT1 mediating Fe uptake were strongly upregulated in the nramp3 nramp4 mutant. Activation of the Fe deficiency response was confirmed by increased ferric chelate reductase activity in the mutant. At early stages, genes important for chloroplast redox control (FSD1, SAPX), Fe homeostasis (FER1, SUFB) and chlorophyll metabolism (HEMA1, NYC1) were downregulated, indicating limited Fe availability in plastids. In contrast, expression of FRO3, encoding a ferric reductase involved in Fe import into the mitochondria, was maintained and Fe-dependent enzymes in the mitochondria were unaffected in nramp3 nramp4. Together these data show that a failure to mobilize Fe stores during germination triggered Fe deficiency responses and strongly affected plastids but not mitochondria.
    Mots-clés : BIOCELL, MINION.

  • D. Carmona-Gutierrez, M. A. Bauer, A. Zimmermann, A. Aguilera, N. Austriaco, K. Ayscough, R. Balzan, S. Bar-Nun, A. Barrientos, P. Belenky, M. Blondel, R. J. Braun, M. Breitenbach, W. C. Burhans, S. Buettner, D. Cavalieri, M. Chang, K. F. Cooper, M. Côrte-Real, V. Costa, C. Cullin, I. Dawes, J. Dengjel, M. B. Dickman, T. Eisenberg, B. Fahrenkrog, N. Fasel, K. - U. Froehlich, A. Gargouri, S. Giannattasio, P. Goffrini, C. W. Gourlay, C. M. Grant, M. T. Greenwood, N. Guaragnella, T. Heger, J. Heinisch, E. Herker, J. M. Herrmann, S. Hofer, A. Jiménez-Ruiz, H. Jungwirth, K. Kainz, D. P. Kontoyiannis, P. Ludovico, S. Manon, E. Martegani, C. Mazzoni, L. A. Megeney, C. Meisinger, J. Nielsen, T. Nystroem, H. D. Osiewacz, T. F. Outeiro, H. - O. Park, T. Pendl, D. Petranovic, S. Picot, P. Polčic, T. Powers, M. Ramsdale, M. Rinnerthaler, P. Rockenfeller, C. Ruckenstuhl, R. Schaffrath, M. Segovia, F. F. Severin, A. Sharon, S. J. Sigrist, C. Sommer-Ruck, M. J. Sousa, J. M. Thevelein, K. Thevissen, V. Titorenko, M. B. Toledano, M. Tuite, F. - N. Voegtle, B. Westermann, J. Winderickx, S. Wissing, S. Woelfl, Z. J. Zhang, R. Y. Zhao, B. Zhou, L. Galluzzi, G. Kroemer, et F. Madeo, « Guidelines and recommendations on yeast cell death nomenclature », Microbial Cell, vol. 5, nᵒ 1, p. 4-31, janv. 2018.

  • E. H. Dawson, T. P. M. Bailly, J. Dos Santos, C. Moreno, M. Devilliers, B. Maroni, C. Sueur, A. Casali, B. Ujvari, F. Thomas, J. Montagne, et F. Mery, « Social environment mediates cancer progression in Drosophila », Nature Communications, vol. 9, nᵒ 1, p. 3574, sept. 2018.
    Résumé : The influence of oncogenic phenomena on the ecology and evolution of animal species is becoming an important research topic. Similar to host-pathogen interactions, cancer negatively affects host fitness, which should lead to the selection of host control mechanisms, including behavioral traits that best minimize the proliferation of malignant cells. Social behavior is suggested to influence tumor progression. While the ecological benefits of sociality in gregarious species are widely acknowledged, only limited data are available on the role of the social environment on cancer progression. Here, we exposed adult Drosophila, with colorectal-like tumors, to different social environments. We show how subtle variations in social structure have dramatic effects on the progression of tumor growth. Finally, we reveal that flies can discriminate between individuals at different stages of tumor development and selectively choose their social environment accordingly. Our study demonstrates the reciprocal links between cancer and social interactions and how sociality may impact health and fitness in animals and its potential implications for disease ecology.
    Mots-clés : BIOCELL, METABO.

  • T. Di Mattia, L. P. Wilhelm, S. Ikhlef, C. Wendling, D. Spehner, Y. Nominé, F. Giordano, C. Mathelin, G. Drin, C. Tomasetto, et F. Alpy, « Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites », EMBO reports, vol. 19, nᵒ 7, juill. 2018.
    Résumé : Membrane contact sites are cellular structures that mediate interorganelle exchange and communication. The two major tether proteins of the endoplasmic reticulum (ER), VAP-A and VAP-B, interact with proteins from other organelles that possess a small VAP-interacting motif, named FFAT [two phenylalanines (FF) in an acidic track (AT)]. In this study, using an unbiased proteomic approach, we identify a novel ER tether named motile sperm domain-containing protein 2 (MOSPD2). We show that MOSPD2 possesses a Major Sperm Protein (MSP) domain which binds FFAT motifs and consequently allows membrane tethering in vitro MOSPD2 is an ER-anchored protein, and it interacts with several FFAT-containing tether proteins from endosomes, mitochondria, or Golgi. Consequently, MOSPD2 and these organelle-bound proteins mediate the formation of contact sites between the ER and endosomes, mitochondria, or Golgi. Thus, we characterized here MOSPD2, a novel tethering component related to VAP proteins, bridging the ER with a variety of distinct organelles.
    Mots-clés : BIOCELL, COAST, endoplasmic reticulum, ER–organelle contact, FFAT motif, membrane contact site, VAP proteins.

  • A. Dreinert, A. Wolf, T. Mentzel, B. Meunier, et M. Fehr, « The cytochrome bc1 complex inhibitor Ametoctradin has an unusual binding mode », Biochimica et Biophysica Acta (BBA) - Bioenergetics, vol. 1859, nᵒ 8, p. 567-576, avr. 2018.
    Résumé : Ametoctradin is an agricultural fungicide that selectively inhibits the cytochrome bc1 complex of oomycetes. Previous spectrophotometric studies using the purified cytochrome bc1 complex from Pythium sp. showed that Ametoctradin binds to the Qo-site of the enzyme. However, as modeling studies suggested a binding mode like that of the substrate ubiquinol, the possibility for a dual Qo- and Qi-site binding mode was left open. In this work, binding studies and enzyme assays with mitochondrial membrane preparations from Pythium sp. and an S. cerevisiae strain with a modified Qi-site were used to investigate further the binding mode of Ametoctradin. The results obtained argue that the compound could bind to both the Qo- and Qi-sites of the cytochrome bc1 complex and that its position or binding pose in the Qi-site differs from that of Cyazofamid and Amisulbrom, the two Qi-site-targeting, anti-oomycetes compounds. Furthermore, the data support the argument that Ametoctradin prefers binding to the reduced cytochrome bc1 complex. Thus, Ametoctradin has an unusual binding mode and further studies with this compound may offer the opportunity to better understand the catalytic cycle of the cytochrome bc1 complex.
    Mots-clés : Ametoctradin, Amisulbrom, BIOCELL, BIOMIT, Cyazofamid, Cytochrome bc(1) complex, Initium, Oomycetes, Respiration inhibitor, Respiratory complex III.

  • G. Dubeaux, J. Neveu, E. Zelazny, et G. Vert, « Metal Sensing by the IRT1 Transporter-Receptor Orchestrates Its Own Degradation and Plant Metal Nutrition », Molecular Cell, vol. 69, nᵒ 6, p. 953-964.e5, mars 2018.
    Résumé : Plant roots forage the soil for iron, the concentration of which can be dramatically lower than those needed for growth. Soil iron uptake uses the broad metal spectrum IRT1 transporter that also transports zinc, manganese, cobalt, and cadmium. Sophisticated iron-dependent transcriptional regulatory mechanisms allow plants to tightly control the abundance of IRT1, ensuring optimal absorption of iron. Here, we uncover that IRT1 acts as a transporter and receptor (transceptor), directly sensing excess of its non-iron metal substrates in the cytoplasm, to regulate its own degradation. Direct metal binding to a histidine-rich stretch in IRT1 triggers its phosphorylation by the CIPK23 kinase and facilitates the subsequent recruitment of the IDF1 E3 ligase. CIPK23-driven phosphorylation and IDF1-mediated lysine-63 polyubiquitination are jointly required for efficient endosomal sorting and vacuolar degradation of IRT1. Thus, IRT1 directly senses elevated non-iron metal concentrations and integrates multiple substrate-dependent regulations to optimize iron uptake and protect plants from highly reactive metals.
    Mots-clés : Arabidopsis, BIOCELL, degradation, metal homeostasis, phosphorylation, plant, receptor, sensing, transceptor, transporter, UBINET, ubiquitin.

  • M. R. Fassad, A. Shoemark, P. le Borgne, F. Koll, M. Patel, M. Dixon, J. Hayward, C. Richardson, E. Frost, L. Jenkins, T. Cullup, E. M. K. Chung, M. Lemullois, A. Aubusson-Fleury, C. Hogg, D. R. Mitchell, A. - M. Tassin, et H. M. Mitchison, « C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia », American Journal of Human Genetics, vol. 102, nᵒ 5, p. 956-972, mai 2018.
    Résumé : Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder characterized by destructive respiratory disease and laterality abnormalities due to randomized left-right body asymmetry. PCD is mostly caused by mutations affecting the core axoneme structure of motile cilia that is essential for movement. Genes that cause PCD when mutated include a group that encode proteins essential for the assembly of the ciliary dynein motors and the active transport process that delivers them from their cytoplasmic assembly site into the axoneme. We screened a cohort of affected individuals for disease-causing mutations using a targeted next generation sequencing panel and identified two unrelated families (three affected children) with mutations in the uncharacterized C11orf70 gene (official gene name CFAP300). The affected children share a consistent PCD phenotype from early life with laterality defects and immotile respiratory cilia displaying combined loss of inner and outer dynein arms (IDA+ODA). Phylogenetic analysis shows C11orf70 is highly conserved, distributed across species similarly to proteins involved in the intraflagellar transport (IFT)-dependant assembly of axonemal dyneins. Paramecium C11orf70 RNAi knockdown led to combined loss of ciliary IDA+ODA with reduced cilia beating and swim velocity. Tagged C11orf70 in Paramecium and Chlamydomonas localizes mainly in the cytoplasm with a small amount in the ciliary component. IFT139/TTC21B (IFT-A protein) and FLA10 (IFT kinesin) depletion experiments show that its transport within cilia is IFT dependent. During ciliogenesis, C11orf70 accumulates at the ciliary tips in a similar distribution to the IFT-B protein IFT46. In summary, C11orf70 is essential for assembly of dynein arms and C11orf70 mutations cause defective cilia motility and PCD.
    Mots-clés : BIOCELL, BIOCIL, dynein, intraflagellar transport, Kartagener syndrome, mutation, Paramecium, primary ciliary dyskinesia.

  • M. R. Fassad, A. Shoemark, M. Legendre, R. A. Hirst, F. Koll, P. le Borgne, B. Louis, F. Daudvohra, M. P. Patel, L. Thomas, M. Dixon, T. Burgoyne, J. Hayes, A. G. Nicholson, T. Cullup, L. Jenkins, S. B. Carr, P. Aurora, M. Lemullois, A. Aubusson-Fleury, J. - F. Papon, C. O'Callaghan, S. Amselem, C. Hogg, E. Escudier, A. - M. Tassin, et H. M. Mitchison, « Mutations in Outer Dynein Arm Heavy Chain DNAH9 Cause Motile Cilia Defects and Situs Inversus », American Journal of Human Genetics, nov. 2018.
    Résumé : Motile cilia move body fluids and gametes and the beating of cilia lining the airway epithelial surfaces ensures that they are kept clear and protected from inhaled pathogens and consequent respiratory infections. Dynein motor proteins provide mechanical force for cilia beating. Dynein mutations are a common cause of primary ciliary dyskinesia (PCD), an inherited condition characterized by deficient mucociliary clearance and chronic respiratory disease coupled with laterality disturbances and subfertility. Using next-generation sequencing, we detected mutations in the ciliary outer dynein arm (ODA) heavy chain gene DNAH9 in individuals from PCD clinics with situs inversus and in one case male infertility. DNAH9 and its partner heavy chain DNAH5 localize to type 2 ODAs of the distal cilium and in DNAH9-mutated nasal respiratory epithelial cilia we found a loss of DNAH9/DNAH5-containing type 2 ODAs that was restricted to the distal cilia region. This confers a reduced beating frequency with a subtle beating pattern defect affecting the motility of the distal cilia portion. 3D electron tomography ultrastructural studies confirmed regional loss of ODAs from the distal cilium, manifesting as either loss of whole ODA or partial loss of ODA volume. Paramecium DNAH9 knockdown confirms an evolutionarily conserved function for DNAH9 in cilia motility and ODA stability. We find that DNAH9 is widely expressed in the airways, despite DNAH9 mutations appearing to confer symptoms restricted to the upper respiratory tract. In summary, DNAH9 mutations reduce cilia function but some respiratory mucociliary clearance potential may be retained, widening the PCD disease spectrum.
    Mots-clés : BIOCELL, BIOCIL, DNAH9, dynein, motile cilia, mutation, primary ciliary dyskinesia, situs inversus, tomography.

  • F. Giordano, « Non-vesicular lipid trafficking at the endoplasmic reticulum–mitochondria interface », Biochemical Society Transactions, p. BST20160185, mars 2018.

  • Y. Guerringue, S. Thomine, et J. - M. Frachisse, « Sensing and transducing forces in plants with MSL10 and DEK1 mechanosensors », FEBS letters, vol. 592, nᵒ 12, p. 1968-1979, mai 2018.
    Résumé : Mechanosensitive (MS) channels behave as microprobes that transduce mechanical tension into electric and ion signals. The plasma membrane anion-permeable channel AtMSL10 belongs to the first family of MS channels (MscS-LIKE) that has been characterized in Arabidopsis thaliana. In the same membrane, a rapidly activated calcium MS channel activity (RMA) associated with the presence of the DEFECTIVE KERNEL1 (AtDEK1) protein has been recently described. In this Review, based on the comparison of the specific properties of AtMSL10 and RMA, we put forward hypotheses on the mechanism of activation of these two channels, their respective roles in signalling and also raise the question of the molecular identity of RMA. Finally, we propose functions for these two channels within the context of plant mechanotransduction.
    Mots-clés : BIOCELL, mechanosensitive channel, mechanotransduction, MINION, plant.

  • C. Jenzer, E. Simionato, C. Largeau, V. Scarcelli, C. Lefebvre, et R. Legouis, « Autophagy mediates phosphatidylserine exposure and phagosome degradation during apoptosis through specific functions of GABARAP/LGG-1 and LC3/LGG-2 », Autophagy, août 2018.
    Résumé : Phagocytosis and macroautophagy/autophagy are 2 processes involved in lysosome-mediated clearance of extracellular and intracellular components, respectively. Recent studies have identified the recruitment of the autophagic protein LC3 during phagocytosis of apoptotic corpses in what is now called LC3-associated phagocytosis (LAP). LAP is a distinct process from autophagy but it relies on some members of the autophagy pathway to allow efficient degradation of the phagocytosed cargo. We investigated whether both LC3/LGG-2 and GABARAP/LGG-1 are involved in phagocytosis of apoptotic corpses during embryonic development of Caenorhabditis elegans. We discovered that both LGG-1 and LGG-2 are involved in the correct elimination of apoptotic corpses, but that they have different functions. lgg-1 and lgg-2 mutants present a delay in phagocytosis of apoptotic cells but genetic analyses indicate that LGG-1 and LGG-2 act upstream and downstream of the engulfment pathways, respectively. Moreover, LGG-1 and LGG-2 display different cellular localizations with enrichment in apoptotic corpses and phagocytic cells, respectively. For both LGG-1 and LGG-2, subcellular localization is vesicular and dependent on UNC-51/ULK1, BEC-1/BECN1 and the lipidation machinery, indicating that their functions during phagocytosis of apoptotic corpses mainly rely on autophagy. Finally, we show that LGG-1 is involved in the exposure of the "eat-me signal" phosphatidylserine at the surface of the apoptotic cell to allow its recognition by the phagocytic cell, whereas LGG-2 is involved in later steps of phagocytosis to allow efficient cell corpse clearance by mediating the maturation/degradation of the phagosome.
    Mots-clés : apoptosis, BIOCELL, Caenorhabditis elegans, cell death, embryogenesis, LAP process, lysosome, OTOFAG, phagosome, phosphatidylserine, VPS-39.

  • P. Junková, M. Daněk, D. Kocourková, J. Brouzdová, K. Kroumanová, E. Zelazny, M. Janda, R. Hynek, J. Martinec, et O. Valentová, « Mapping of Plasma Membrane Proteins Interacting With Arabidopsis thaliana Flotillin 2 », Frontiers in Plant Science, vol. 9, p. 991, 2018.
    Résumé : Arabidopsis flotillin 2 (At5g25260) belongs to the group of plant flotillins, which are not well characterized. In contrast, metazoan flotillins are well known as plasma membrane proteins associated with membrane microdomains that act as a signaling hub. The similarity of plant and metazoan flotillins, whose functions most likely consist of affecting other proteins via protein-protein interactions, determines the necessity of detecting their interacting partners in plants. Nevertheless, identifying the proteins that form complexes on the plasma membrane is a challenging task due to their low abundance and hydrophobic character. Here we present an approach for mapping Arabidopsis thaliana flotillin 2 plasma membrane interactors, based on the immunoaffinity purification of crosslinked and enriched plasma membrane proteins with mass spectrometry detection. Using this approach, 61 proteins were enriched in the AtFlot-GFP plasma membrane fraction, and 19 of them were proposed to be flotillin 2 interaction partners. Among our proposed partners of Flot2, proteins playing a role in the plant response to various biotic and abiotic stresses were detected. Additionally, the use of the split-ubiquitin yeast system helped us to confirm that plasma-membrane ATPase 1, early-responsive to dehydration stress protein 4, syntaxin-71, harpin-induced protein-like 3, hypersensitive-induced response protein 2 and two aquaporin isoforms interact with flotillin 2 directly. Based on the results of our study and the reported properties of Flot2 interactors, we propose that Flot2 complexes may be involved in plant-pathogen interactions, water transport and intracellular trafficking.
    Mots-clés : Arabidopsis flotillin 2, BIOCELL, immunopurification, intracellular trafficking, mass spectrometry, plant–pathogen interaction, protein–protein interactions, split-ubiquitin yeast system, UBINET, water transport.

  • A. Krieger-Liszkay et S. Thomine, « Importing Manganese into the Chloroplast: Many Membranes to Cross », Molecular Plant, vol. 11, nᵒ 9, p. 1109-1111, août 2018.
    Mots-clés : arabidopsis, B3S, BIOCELL, cells, homeostasis, MINION, MROP, photosynthesis, photosystem-ii, protein.

  • V. Lafont, H. - A. Michaud, et N. Bonnefoy, « CD73: a new biomarker in triple-negative breast cancer », Translational Cancer Research, vol. 7, nᵒ 5, p. S594-S596, mai 2018.
    Résumé : Triple-negative breast cancer (TNBC) constitute 10–20% of all breast cancers and are characterized by the lack of hormone receptors (estrogen and progesterone receptors) and HER2/neu expression (1). TNBC are not eligible to hormonotherapy and Herceptin/trastuzumab targeted therapy and are generally associated with poor clinical outcome (2). Anthracycline/taxane-based neoadjuvant chemotherapy is the primary systemic treatment but resistance to this treatment is common and the identification of new potential therapeutic molecules is required to improve the outcome of TNBC patients.
    Mots-clés : BIOCELL, BIOMIT.

  • A. Maréchal, A. M. Hartley, T. P. Warelow, B. Meunier, et P. R. Rich, « Comparison of redox and ligand binding behaviour of yeast and bovine cytochrome c oxidases using FTIR spectroscopy », Biochimica et Biophysica Acta (BBA) - Bioenergetics, mai 2018.
    Résumé : Redox and CO photolysis FTIR spectra of yeast cytochrome c oxidase WT and mutants are compared to those from bovine and P. denitrificans CcOs in order to establish common functional features. All display changes that can be assigned to their E242 (bovine numbering) equivalent and to weakly H-bonded water molecules. The additional redox-sensitive band reported at 1736 cm-1 in bovine CcO and previously assigned to D51 is absent from yeast CcO and couldn't be restored by introduction of a D residue at the equivalent position of the yeast protein. Redox spectra of yeast CcO also show much smaller changes in the amide I region, which may relate to structural differences in the region around D51 and the subunit I/II interface.
    Mots-clés : BIOCELL, BIOMIT, Carboxyl groups, Cytochrome c oxidase, Infrared spectroscopy, Mitochondria, Oxidoreduction, Site-directed mutagenesis.

  • J. Marion, R. Le Bars, L. Besse, H. Batoko, et B. Satiat-Jeunemaitre, « Multiscale and Multimodal Approaches to Study Autophagy in Model Plants », Cells, vol. 7, nᵒ 1, janv. 2018.
    Résumé : Autophagy is a catabolic process used by eukaryotic cells to maintain or restore cellular and organismal homeostasis. A better understanding of autophagy in plant biology could lead to an improvement of the recycling processes of plant cells and thus contribute, for example, towards reducing the negative ecological consequences of nitrogen-based fertilizers in agriculture. It may also help to optimize plant adaptation to adverse biotic and abiotic conditions through appropriate plant breeding or genetic engineering to incorporate useful traits in relation to this catabolic pathway. In this review, we describe useful protocols for studying autophagy in the plant cell, taking into account some specificities of the plant model.
    Mots-clés : Arabidopsis, autophagosome, Autophagy, autophagy assays, BIOCELL, CYTO, DYNBSJ, methods, PHOT, plant cells, Tobacco.

  • K. Mishev, Q. Lu, B. Denoo, F. Peurois, W. Dejonghe, J. Hullaert, R. De Rycke, S. Boeren, M. Bretou, S. De Munck, I. Sharma, K. Goodman, K. Kalinowska, V. Storme, L. S. L. Nguyen, A. Drozdzecki, S. Martins, W. Nerinckx, D. Audenaert, G. Vert, A. Madder, M. S. Otegui, E. Isono, S. N. Savvides, W. Annaert, S. De Vries, J. Cherfils, J. Winne, et E. Russinova, « Nonselective Chemical Inhibition of Sec7 Domain-Containing ARF GTPase Exchange Factors », Plant Cell, vol. 30, nᵒ 10, p. 2573-2593, oct. 2018.
    Résumé : Small GTP-binding proteins from the ADP-ribosylation factor (ARF) family are important regulators of vesicle formation and cellular trafficking in all eukaryotes. ARF activation is accomplished by a protein family of guanine nucleotide exchange factors (GEFs) that contain a conserved catalytic Sec7 domain. Here, we identified and characterized Secdin, a small-molecule inhibitor of Arabidopsis thaliana ARF-GEFs. Secdin application caused aberrant retention of plasma membrane (PM) proteins in late endosomal compartments, enhanced vacuolar degradation, impaired protein recycling, and delayed secretion and endocytosis. Combined treatments with Secdin and the known ARF-GEF inhibitor Brefeldin A (BFA) prevented the BFA-induced PM stabilization of the ARF-GEF GNOM, impaired its translocation from the Golgi to the trans-Golgi network/early endosomes, and led to the formation of hybrid endomembrane compartments reminiscent of those in ARF-GEF-deficient mutants. Drug affinity-responsive target stability assays revealed that Secdin, unlike BFA, targeted all examined Arabidopsis ARF-GEFs, but that the interaction was probably not mediated by the Sec7 domain because Secdin did not interfere with the Sec7 domain-mediated ARF activation. These results show that Secdin and BFA affect their protein targets through distinct mechanisms, in turn showing the usefulness of Secdin in studies in which ARF-GEF-dependent endomembrane transport cannot be manipulated with BFA.
    Mots-clés : arabidopsis-thaliana, BIOCELL, brefeldin-a, endomembrane trafficking, golgi network/early endosome, plant-cells, plasma-membrane, protein complexes, receptor kinase bri1, small molecules, UBINET, wide analysis.

  • M. Mishra, H. Jiang, H. A. Chawsheen, M. Gerard, M. B. Toledano, et Q. Wei, « Nrf2-activated expression of sulfiredoxin contributes to urethane-induced lung tumorigenesis », Cancer Letters, vol. 432, p. 216-226, sept. 2018.
    Résumé : Lung cancer is the leading cause of cancer death worldwide. Cigarette smoking and exposure to chemical carcinogens are among the risk factors of lung tumorigenesis. In this study, we found that cigarette smoke condensate and urethane significantly stimulated the expression of sulfiredoxin (Srx) at the transcript and protein levels in cultured normal lung epithelial cells, and such stimulation was mediated through the activation of nuclear related factor 2 (Nrf2). To study the role of Srx in lung cancer development in vivo, mice with Srx wildtype, heterozygous or knockout genotype were subjected to the same protocol of urethane treatment to induce lung tumors. By comparing tumor multiplicity and volume between groups of mice with different genotype, we found that Srx knockout mice had a significantly lower number and smaller size of lung tumors. Mechanistically, we demonstrated that loss of Srx led to a decrease of tumor cell proliferation as well as an increase of tumor cell apoptosis. These data suggest that Srx may have an oncogenic role that contributes to the development of lung cancer in smokers or urethane-exposed human subjects.
    Mots-clés : Antioxidant, BIOCELL, Cell growth and proliferation, Oxidative stress, Peroxiredoxins, Signal transduction, SOC.

  • P. Mounkoro, T. Michel, R. Benhachemi, G. Surpateanu, B. I. Iorga, N. Fisher, et B. Meunier, « Mitochondrial complex III Qi -site inhibitor resistance mutations found in laboratory selected mutants and field isolates », Pest Management Science, nov. 2018.
    Résumé : BACKGROUND: Complex III inhibitors targeting the Qi -site have been known for decades; some are used or are being developed as anti-microbial compounds. Target site resistance mutations have been reported in laboratory-selected mutants and in field isolates. Here we present a brief over-view of mutations found in laboratory selected resistant mutants. We also provide a study of mutations observed in field isolates of Plasmopara viticola, in particular the ametoctradin resistance substitution, S34L that we analyzed in the yeast model. RESULTS: The survey of laboratory mutants showed that resistance could be caused by a large number of substitutions in the Qi -site. Four residues seemed key in term of resistance, N31, G37, L198 and K228. Using yeast, we analyzed the effect of the ametoctradin resistance substitution S34L reported in field isolates of P.viticola. We showed that S34L caused a high level of resistance combined with a loss of complex III activity and growth competence. CONCLUSION: The use of single site QiIs is expected to result in the selection of resistant mutants. However if the substitution is associated with a fitness penalty, as it could be the case with S34L, resistance development might not be an insuperable obstacle but careful monitoring is required. This article is protected by copyright. All rights reserved.
    Mots-clés : bc1 complex, BIOCELL, BIOMIT, fungicides, QiI, resistance, target site mutation, yeast model.

  • D. Naquin, C. Panozzo, G. Dujardin, E. van Dijk, Y. d'Aubenton-Carafa, et C. Thermes, « Complete Sequence of the Intronless Mitochondrial Genome of the Saccharomyces cerevisiae Strain CW252 », Genome Announcements, vol. 6, nᵒ 17, avr. 2018.
    Résumé : The mitochondrial genomes of Saccharomyces cerevisiae strains contain up to 13 introns. An intronless recombinant genome introduced into the nuclear background of S. cerevisiae strain W303 gave the S. cerevisiae CW252 strain, which is used to model mitochondrial respiratory pathologies. The complete sequence of this mitochondrial genome was obtained using a hybrid assembling methodology.
    Mots-clés : BIOCELL, BIOMIT, NGS, PF.

  • M. Pottier, J. Dumont, C. Masclaux-Daubresse, et S. Thomine, « Autophagy is essential for optimal Fe translocation to seeds in Arabidopsis », Journal of Experimental Botany, nov. 2018.
    Résumé : Micronutrient deficiencies affect a large part of the world population. They are mostly due to the consumption of grains with insufficient content of Fe or Zn. Both de novo uptake by roots and recycling from leaves may provide seeds with nutrients. Autophagy, which is a conserved mechanism for nutrient recycling in eukaryotes, was shown to be involved in nitrogen remobilization to seeds. Here, we have investigated the role of this mechanism in micronutrient translocation to seeds. We found that several Arabidopsis thaliana plants impaired in autophagy display defects in nutrient remobilization to seeds. In atg5-1 mutant, which is completely defective in autophagy, the efficiency of Fe translocation from vegetative organs to seeds was severely decreased even when Fe was provided during seed formation. Combining atg5-1 with sid2 mutation that counteracts premature senescence associated to autophagy deficiency and using 57Fe pulse labeling, we could propose a two-step mechanism in which iron taken up de novo during seed formation is first accumulated in vegetative organs and subsequently remobilized to seeds. Finally, we showed that translocations of zinc and manganese to seeds are also dependent on autophagy. Fine tuning autophagy during seed formation opens therefore new possibilities to improve micronutrient remobilization to seeds.
    Mots-clés : BIOCELL, MINION.

  • S. Rahuel-Clermont et M. B. Toledano, « Parsing protein sulfinic acid switches », Nature Chemical Biology, vol. 14, nᵒ 11, p. 991-993, nov. 2018.
    Mots-clés : BIOCELL, cysteine, peroxiredoxin, SOC, sulfiredoxin.

  • N. Romero-Barrios et G. Vert, « Proteasome-independent functions of lysine-63 polyubiquitination in plants », The New Phytologist, vol. 217, nᵒ 3, p. 995-1011, févr. 2018.
    Résumé : Contents Summary 995 I. Introduction 995 II. The plant Ub machinery 996 III. From Ub to Ub linkage types in plants 997 IV. Increasing analytical resolution for K63 polyUb in plants 998 V. How to build K63 polyUb chains? 998 VI. Cellular roles of K63 polyUb in plants 999 VII. Physiological roles of K63 polyUb in plants 1004 VIII. Future perspectives: towards the next level of the Ub code 1006 Acknowledgements 1006 References 1007 SUMMARY: Ubiquitination is a post-translational modification essential for the regulation of eukaryotic proteins, having an impact on protein fate, function, localization or activity. What originally appeared to be a simple system to regulate protein turnover by the 26S proteasome is now known to be the most intricate regulatory process cells have evolved. Ubiquitin can be arranged in countless chain assemblies, triggering various cellular outcomes. Polyubiquitin chains using lysine-63 from ubiquitin represent the second most abundant type of ubiquitin modification. Recent studies have exposed their common function in proteasome-independent functions in non-plant model organisms. The existence of lysine-63 polyubiquitination in plants is, however, only just emerging. In this review, we discuss the recent advances on the characterization of ubiquitin chains and the molecular mechanisms driving the formation of lysine-63-linked ubiquitin modifications. We provide an overview of the roles associated with lysine-63 polyubiquitination in plant cells in the light of what is known in non-plant models. Finally, we review the crucial roles of lysine-63 polyubiquitin-dependent processes in plant growth, development and responses to environmental conditions.
    Mots-clés : Autophagy, BIOCELL, UBINET.

  • L. Shi, F. Koll, O. Arnaiz, et J. Cohen, « The Ciliary Protein IFT57 in the Macronucleus of Paramecium », The Journal of Eukaryotic Microbiology, vol. 65, nᵒ 1, p. 12-27, janv. 2018.
    Résumé : The intraflagellar transport IFT57 protein is essential for ciliary growth and maintenance. Also known as HIPPI, human IFT57 can be translocated to the nucleus via a molecular partner of the Huntingtin, Hip1, inducing gene expression changes. In Paramecium tetraurelia, we identified four IFT57 genes forming two subfamilies IFT57A/B and IFT57C/D arising from whole genome duplications. The depletion of proteins of the two subfamilies induced ciliary defects and IFT57A and IFT57C localized in basal bodies and cilia. We observed that IFT57A, but not IFT57C, is also present in the macronucleus and able to traffic toward the developing anlage during autogamy. Analysis of chimeric IFT57A-IFT57C-GFP-tagged proteins allowed us to identify a region of IFT57A necessary for nuclear localization. We studied the localization of the unique IFT57 protein of Paramecium caudatum, a species, which diverged from P. tetraurelia before the whole genome duplications. The P. caudatumIFT57C protein was excluded from the nucleus. We also analyzed whether the overexpression of IFT57A in Paramecium could affect gene transcription as the human protein does in HeLa cells. The expression of some genes was indeed affected by overexpression of IFT57A, but the set of affected genes poorly overlaps the set of genes affected in human cells.
    Mots-clés : ANGE, BIOCELL, BIOCIL, cilia, DBG, HIPPI, IFT57 /HIPPI, intraflagellar transport, intraflagellar transport (IFT), Macronucleus, MICMAC, Paramecium.

  • Z. Song, B. I. Iorga, P. Mounkoro, N. Fisher, et B. Meunier, « The antimalarial compound ELQ-400 is an unusual inhibitor of the <i>bc</i> <sub>1</sub> complex, targeting both <i>Q</i> <sub>o</sub> and <i>Q</i> <sub>i</sub> sites », FEBS Letters, mars 2018.

  • S. Merlot, V. Sanchez Garcia de la Torre, et M. Hanikenne, « Physiology and Molecular Biology of Trace Element Hyperaccumulation », in Agromining: Farming for Metals, A. Van der Ent, G. Echevarria, A. J. M. Baker, et J. L. Morel, Éd. Cham: Springer International Publishing, 2018, p. 93-116.


  • A. Agorio, J. Giraudat, M. W. Bianchi, J. Marion, C. Espagne, L. Castaings, F. Lelièvre, C. Curie, S. Thomine, et S. Merlot, « Phosphatidylinositol 3-phosphate–binding protein AtPH1 controls the localization of the metal transporter NRAMP1 in Arabidopsis », Proceedings of the National Academy of Sciences, p. 201702975, avr. 2017.
    Mots-clés : BIOCELL, DYNBSJ, late endosome, metal transport, MINION, NRAMP, phosphatidylinositol 3-phosphate, vacuole.

  • S. Ait-El-Mkadem, M. Dayem-Quere, M. Gusic, A. Chaussenot, S. Bannwarth, B. François, E. C. Genin, K. Fragaki, C. L. M. Volker-Touw, C. Vasnier, V. Serre, K. L. I. van Gassen, F. Lespinasse, S. Richter, G. Eisenhofer, C. Rouzier, F. Mochel, A. De Saint-Martin, M. - T. Abi Warde, M. G. M. de Sain-van der Velde, J. J. M. Jans, J. Amiel, Z. Avsec, C. Mertes, T. B. Haack, T. Strom, T. Meitinger, P. E. Bonnen, R. W. Taylor, J. Gagneur, P. M. van Hasselt, A. Rötig, A. Delahodde, H. Prokisch, S. A. Fuchs, et V. Paquis-Flucklinger, « Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy », American Journal of Human Genetics, vol. 100, nᵒ 1, p. 151-159, 2017.

  • A. Arnal, C. Jacqueline, B. Ujvari, L. Leger, C. Moreno, D. Faugere, A. Tasiemski, C. Boidin-Wichlacz, D. Misse, F. Renaud, J. Montagne, A. Casali, B. Roche, F. Mery, et F. Thomas, « Cancer brings forward oviposition in the fly Drosophila melanogaster », Ecology and Evolution, vol. 7, nᵒ 1, p. 272-276, janv. 2017.
    Résumé : Hosts often accelerate their reproductive effort in response to a parasitic infection, especially when their chances of future reproduction decrease with time from the onset of the infection. Because malignancies usually reduce survival, and hence potentially the fitness, it is expected that hosts with early cancer could have evolved to adjust their life-history traits to maximize their immediate reproductive effort. Despite the potential importance of these plastic responses, little attention has been devoted to explore how cancers influence animal reproduction. Here, we use an experimental setup, a colony of genetically modified flies Drosophila melanogaster which develop colorectal cancer in the anterior gut, to show the role of cancer in altering life-history traits. Specifically, we tested whether females adapt their reproductive strategy in response to harboring cancer. We found that flies with cancer reached the peak period of oviposition significantly earlier (i.e., 2 days) than healthy ones, while no difference in the length and extent of the fecundity peak was observed between the two groups of flies. Such compensatory responses to overcome the fitness-limiting effect of cancer could explain the persistence of inherited cancer-causing mutant alleles in the wild.
    Mots-clés : BIOCELL, cancer, fecundity, life‐history strategy, METABO, reproduction.

  • A. Aubusson-Fleury, G. Balavoine, M. Lemullois, K. Bouhouche, J. Beisson, et F. Koll, « Centrin diversity and basal body patterning across evolution: new insights from Paramecium », Biology Open, avr. 2017.
    Résumé : First discovered in unicellular eukaryotes, centrins play crucial roles in basal body duplication and anchoring mechanisms. While the evolutionary status of the founding members of the family, Centrin2/Vfl2 and Centrin3/cdc31 has long been investigated, the evolutionary origin of other members of the family has received less attention. Using a phylogeny of ciliate centrins, we identify two other centrin families, the ciliary centrins and the centrins present in the contractile filaments (ICL centrins). In this paper, we carry on the functional analysis of still not well known centrins, the ICL1e subfamily identified in Paramecium, and show their requirement for correct basal body anchoring through interactions with Centrin2 and Centrin3. Using Paramecium as well as an Eukaryote-wide sampling of centrins from completely sequenced genomes, we revisited the evolutionary story of centrins. Their phylogeny shows that the centrins associated with the ciliate contractile filaments are widespread in eukaryotic lineages and could be as ancient as Centrin2 and Centrin3.
    Mots-clés : basal body anchoring, basal body assembly, BIOCELL, BIOCIL, centrin evolution, Ciliary centrins, ciliated epithelia polarity.

  • H. Bengueddach, M. Lemullois, A. Aubusson-Fleury, et F. Koll, « Basal body positioning and anchoring in the multiciliated cell Paramecium tetraurelia: roles of OFD1 and VFL3 », Cilia, vol. 6, nᵒ 1, 2017.

  • A. Bersweiler, B. D'Autréaux, H. Mazon, A. Kriznik, G. Belli, A. Delaunay-Moisan, M. B. Toledano, et S. Rahuel-Clermont, « A scaffold protein that chaperones a cysteine-sulfenic acid in H2O2 signaling », Nature Chemical Biology, juin 2017.
    Résumé : In Saccharomyces cerevisiae, Yap1 regulates an H2O2-inducible transcriptional response that controls cellular H2O2 homeostasis. H2O2 activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with H2O2, Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages into either an intermolecular disulfide with Yap1, leading to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. How the first of these two competing reactions, which is kinetically unfavorable, occurs was previously unknown. We show that the Yap1-binding protein Ybp1 brings together Orp1 and Yap1 into a ternary complex that selectively activates condensation of the Orp1 sulfenylated cysteine with one of the six Yap1 cysteines while inhibiting Orp1 intramolecular disulfide formation. We propose that Ybp1 operates as a scaffold protein and as a sulfenic acid chaperone to provide specificity in the transfer of oxidizing equivalents by a reactive sulfenic acid species.
    Mots-clés : BIOCELL, SOC.

  • K. Bodvard, K. Peeters, F. Roger, N. Romanov, A. Igbaria, N. Welkenhuysen, G. Palais, W. Reiter, M. B. Toledano, M. Käll, et M. Molin, « Light-sensing via hydrogen peroxide and a peroxiredoxin », Nature Communications, vol. 8, p. 14791, mars 2017.

  • S. C. Brown, M. Bourge, N. Maunoury, M. Wong, M. W. Bianchi, S. Lepers-Andrzejewski, P. Besse, S. Siljak-Yakovlev, M. Dron, et B. Satiat-Jeunemaître, « DNA remodelling by Strict Partial Endoreplication in orchids, an original process in the plant kingdom », Genome Biology and Evolution, avr. 2017.
    Résumé : DNA remodelling during endoreplication appears to be a strong developmental characteristic in orchids. In this study, we analysed DNA content and nuclei in 41 species of orchids to further map the genome evolution in this plant family. We demonstrate that the DNA remodelling observed in 36 out of 41 orchids studied corresponds to strict partial endoreplication. Such process is developmentally regulated in each wild species studied. Cytometry data analyses allowed us to propose a model where nuclear states 2C, 4E, 8E, etc. form a series comprising a fixed proportion, the euploid genome 2C, plus 2 to 32 additional copies of a complementary part of the genome. The fixed proportion ranged from 89% of the genome in Vanilla mexicana down to 19% in V. pompona, the lowest value for all 148 orchids reported. Insterspecific hybridisation did not suppress this phenomenon. Interestingly, this process was not observed in mass-produced epiphytes. Nucleolar volumes grow with the number of endocopies present, coherent with high transcription activity in endoreplicated nuclei. Our analyses suggest species-specific chromatin rearrangement. Towards understanding endoreplication, V. planifolia constitutes a tractable system for isolating the genomic sequences that confer an advantage via endoreplication from those that apparently suffice at diploid level.
    Mots-clés : BIOCELL, CYTO, cytogenetics, cytometry, DYNBSJ, endoreplication, genome imbalance, Genome Size, IMAGIF, MINION, PF, PHOT, Vanilla.

  • S. Chardonnet, T. Bessiron, C. I. Ramos, R. Dammak, M. - A. Richard, C. Boursier, C. Cadillac, F. M. Coquelle, S. Bossi, F. Ango, P. Le Maréchal, P. Decottignies, C. Berrier, H. McLean, et H. Daniel, « Native metabotropic glutamate receptor 4 depresses synaptic transmission through an unusual Gαq transduction pathway », Neuropharmacology, avr. 2017.
    Résumé : In cerebellar cortex, mGlu4 receptors located on parallel fibers play an essential role in normal motor function, but the molecular mechanisms involved are not yet completely understood. Using a strategy combining biochemical and electrophysiological approaches in the rodent cerebellum, we demonstrate that presynaptic mGlu4 receptors control synaptic transmission through an atypical activation of Gαq proteins. First, the Gαq subunit, PLC and PKC signaling proteins present in cerebellar extracts are retained on affinity chromatography columns grafted with different sequences of the cytoplasmic domain of mGlu4 receptor. The i2 loop and the C terminal domain were used as baits, two domains that are known to play a pivotal role in coupling selectivity and efficacy. Second, in situ proximity ligation assays show that native mGlu4 receptors and Gαq subunits are in close physical proximity in cerebellar cortical slices. Finally, electrophysiological experiments demonstrate that the molecular mechanisms underlying mGlu4 receptor-mediated inhibition of transmitter release at cerebellar Parallel Fiber (PF) - Molecular Layer Interneuron (MLI) synapses involves the Gαq-PLC signaling pathway. Taken together, our results provide compelling evidence that, in the rodent cerebellar cortex, mGlu4 receptors act by coupling to the Gαq protein and PLC effector system to reduce glutamate synaptic transmission.
    Mots-clés : BIOCELL, Cerebellar cortex, DYNBSJ, G protein, Molecular layer interneurons, Presynaptic metabotropic glutamate receptor 4, Signaling pathway, Synaptic transmission.

  • Y. Chen, V. Scarcelli, et R. Legouis, « Approaches for Studying Autophagy in Caenorhabditis elegans », Cells, vol. 6, nᵒ 3, p. 27, août 2017.
    Mots-clés : aggrephagy, BIOCELL, C. elegans, Electron Microscopy, Genetics, in vivo imaging, LGG-1, LGG-2, mitophagy, OTOFAG.

  • A. Delaunay-Moisan, A. Ponsero, et M. Toledano, « Reexamining the function of glutathione in oxidative protein folding and secretion », Antioxidants & Redox Signaling, août 2017.
    Résumé : SIGNIFICANCE: Disturbance of glutathione metabolism is a hallmark of numerous diseases, yet glutathione functions are poorly understood. One key to this question is to consider its functional compartmentation. In the endoplasmic reticulum (ER), protein folding involves disulfide bond formation catalyzed by the thiol oxidase Ero1 and proteins from the disulfide isomerase family (PDI). GSH competes with substrates for oxidation by Ero1, but its requirement for ER oxidative protein folding is questioned. Recent Advances: Oxidative protein folding has been thoroughly dissected over the last decades, and its actors and their mode of action elucidated. Genetically-encoded GSH probes have recently provided an access to subcellular redox metabolism, including the ER. CRITICAL ISSUES: Of the few often-contradictory models of the role of GSH in the ER, the most popular suggest it serves as reducing power. Yet, as a reductant, GSH also activates Ero1, which questions how glutathione can nevertheless support protein reduction. Hence, whether glutathione operates in the ER as a reductant, an oxidant, or just as a "blank" compound mirroring ER/periplasm redox activity is a highly debated question, further stimulated by the puzzling occurrence of glutathione in the E. coli periplasmic "secretory" compartment, aside of the Dsb thiol-reducing and oxidase pathways. FUTURE DIRECTIONS: Addressing the mechanisms controlling glutathione traffic in and out the ER/periplasm and its recycling will help address glutathione function in secretion. In addition, as thioredoxin reductase was recently implicated in ER oxidative protein folding, the relative contribution of each of these two reducing pathways should now be addressed.
    Mots-clés : BIOCELL, SOC.

  • E. Diatloff, E. S. Mace, D. R. Jordan, S. Filleur, S. Tai, S. Schmidt, et I. D. Godwin, « The vegetative nitrogen response of sorghum lines containing different alleles for nitrate reductase and glutamate synthase », Molecular Breeding, vol. 37, nᵒ 11, 2017.

  • M. J. Domingues, J. Martinez-Sanz, L. Papon, L. Larue, L. Mouawad, et J. Bonaventure, « Structure-based mutational analysis of ICAT residues mediating negative regulation of β-catenin co-transcriptional activity », PloS One, vol. 12, nᵒ 3, p. e0172603, 2017.
    Résumé : ICAT (Inhibitor of β-CAtenin and TCF) is a small acidic protein that negatively regulates β-catenin co-transcriptional activity by competing with TCF/LEF factors in their binding to β-catenin superhelical core. In melanoma cells, ICAT competes with LEF1 to negatively regulate the M-MITF and NEDD9 target genes. The structure of ICAT consists of two domains: the 3-helix bundle N-terminal domain binds to β-catenin Armadillo (Arm) repeats 10-12 and the C-terminal tail binds to Arm repeats 5-9. To elucidate the structural mechanisms governing ICAT/β-catenin interactions in melanoma cells, three ICAT residues Y15, K19 and V22 in the N-terminal domain, contacting hydrophobic β-catenin residue F660, were mutated and interaction was assessed by immunoprecipitation. Despite the moderate hydrophobicity of the contact, its removal completely abolished the interaction. In the ICAT C-terminal tail consensus sequence, neutralization of the electrostatic interactions between residues D66, E75 and β-catenin residues K435, K312, coupled to deletion of the hydrophobic contact between F71 and β-catenin R386, markedly reduced, but failed to abolish the ICAT-mediated negative regulation of M-MITF and NEDD9 promoters. We conclude that in melanoma cells, anchoring of ICAT N-terminal domain to β-catenin through the hook made by residue F660, trapped in the pincers formed by ICAT residues Y15 and V22, is crucial for stabilizing the ICAT/β-catenin complex. This is a prerequisite for binding of the consensus peptide to Arm repeats 5-9 and competition with LEF1. Differences between ICAT and LEF1 in their affinity for β-catenin may rely on the absence in ICAT of hydrophilic residues between D66 and F71.
    Mots-clés : BIOCELL, BIOCIL.

  • G. Dubeaux et G. Vert, « Zooming into plant ubiquitin-mediated endocytosis », Current Opinion in Plant Biology, vol. 40, p. 56-62, juill. 2017.
    Résumé : Endocytosis in plants plays an essential role, not only for basic cellular functions but also for growth, development, and environmental responses. Over the past few years, ubiquitin emerged as a major signal triggering the removal of plasma membrane proteins from the cell surface and promoting their vacuolar targeting. Detailed genetic, biochemical and imaging studies have provided initial insights into the precise mechanisms and roles of ubiquitin-mediated endocytosis in plants. Here, we summarize the present state of knowledge about the machinery involved in plant ubiquitin-mediated endocytosis and how this is coordinated in time and space to control the internalization and the endosomal sorting of endocytosed proteins.
    Mots-clés : BIOCELL, UBINET.

  • C. Eisenach, U. Baetz, N. V. Huck, J. Zhang, A. De Angeli, G. J. M. Beckers, et E. Martinoia, « ABA-Induced Stomatal Closure Involves ALMT4, a Phosphorylation-Dependent Vacuolar Anion Channel of Arabidopsis », The Plant Cell, vol. 29, nᵒ 10, p. 2552-2569, 2017.

  • C. Eisenach et A. De Angeli, « Ion Transport at the Vacuole During Stomatal Movements », Plant Physiology, p. pp.00130.2017, avr. 2017.

  • R. Enrique Gomez, J. Joubès, N. Valentin, H. Batoko, B. Satiat-Jeunemaître, et A. Bernard, « Lipids in membrane dynamics during autophagy in plants », Journal of Experimental Botany, nov. 2017.
    Résumé : Autophagy is a critical pathway for plant adaptation to stress. Macroautophagy relies on the biogenesis of a specialized membrane named the phagophore that maturates into a double membrane vesicle. Proteins and lipids act synergistically to promote membrane structure and functions, yet research on autophagy has mostly focused on autophagy-related proteins while knowledge of supporting lipids in the formation of autophagic membranes remains scarce. This review expands on studies in plants with examples from other organisms to present and discuss our current understanding of lipids in membrane dynamics associated with the autophagy pathway in plants.
    Mots-clés : Arabidopsis, autophagy, BIOCELL, DYNBSJ, homeostasis, lipids, membrane, Plant.

  • A. Glatigny, P. Gambette, A. Bourand-Plantefol, G. Dujardin, et M. - H. Mucchielli-Giorgi, « Development of an in silico method for the identification of subcomplexes involved in the biogenesis of multiprotein complexes in Saccharomyces cerevisiae », BMC systems biology, vol. 11, nᵒ 1, p. 67, juill. 2017.
    Résumé : BACKGROUND: Large sets of protein-protein interaction data coming either from biological experiments or predictive methods are available and can be combined to construct networks from which information about various cell processes can be extracted. We have developed an in silico approach based on these information to model the biogenesis of multiprotein complexes in the yeast Saccharomyces cerevisiae. RESULTS: Firstly, we have built three protein interaction networks by collecting the protein-protein interactions, which involved the subunits of three complexes, from different databases. The protein-protein interactions come from different kinds of biological experiments or are predicted. We have chosen the elongator and the mediator head complexes that are soluble and exhibit an architecture with subcomplexes that could be functional modules, and the mitochondrial bc 1 complex, which is an integral membrane complex and for which a late assembly subcomplex has been described. Secondly, by applying a clustering strategy to these networks, we were able to identify subcomplexes involved in the biogenesis of the complexes as well as the proteins interacting with each subcomplex. Thirdly, in order to validate our in silico results for the cytochrome bc1 complex we have analysed the physical interactions existing between three subunits by performing immunoprecipitation experiments in several genetic context. CONCLUSIONS: For the two soluble complexes (the elongator and mediator head), our model shows a strong clustering of subunits that belong to a known subcomplex or module. For the membrane bc 1 complex, our approach has suggested new interactions between subunits in the early steps of the assembly pathway that were experimentally confirmed. Scripts can be downloaded from the site: .
    Mots-clés : BIM, BIOCELL, BIOMIT, Complex assembly, DBG, Graph clustering, PPI network, Protein complex, Protein-protein interactions, Subcomplex.

  • Y. Goulev, S. Morlot, A. Matifas, B. Huang, M. Molin, M. B. Toledano, et G. Charvin, « Nonlinear feedback drives homeostatic plasticity in H2O2 stress response », eLife, vol. 6, avr. 2017.
    Résumé : Homeostatic systems that rely on genetic regulatory networks are intrinsically limited by the transcriptional response time, which may restrict a cell's ability to adapt to unanticipated environmental challenges. To bypass this limitation, cells have evolved mechanisms whereby exposure to mild stress increases their resistance to subsequent threats. However, the mechanisms responsible for such adaptive homeostasis remain largely unknown. Here, we used live-cell imaging and microfluidics to investigate the adaptive response of budding yeast to temporally controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is a systems-level property resulting from nonlinearity of H2O2 scavenging by peroxiredoxins and our study reveals that this regulatory scheme induces a striking hormetic effect of extracellular H2O2 stress on replicative longevity. Our study thus provides a novel quantitative framework bridging the molecular architecture of a cellular homeostatic system to the emergence of nonintuitive adaptive properties.
    Mots-clés : BIOCELL, cell biology, Computational Biology, S. cerevisiae, SOC, systems biology.

  • F. Habarou, Y. Hamel, T. B. Haack, R. G. Feichtinger, E. Lebigot, I. Marquardt, K. Busiah, C. Laroche, M. Madrange, C. Grisel, C. Pontoizeau, M. Eisermann, A. Boutron, D. Chrétien, B. Chadefaux-Vekemans, R. Barouki, C. Bole-Feysot, P. Nitschke, N. Goudin, N. Boddaert, I. Nemazanyy, A. Delahodde, S. Kölker, R. J. Rodenburg, G. C. Korenke, T. Meitinger, T. M. Strom, H. Prokisch, A. Rotig, C. Ottolenghi, J. A. Mayr, et P. de Lonlay, « Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy », American Journal of Human Genetics, vol. 101, nᵒ 2, p. 283-290, août 2017.
    Résumé : Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2.
    Mots-clés : BIOCELL, encephalopathy, FDMITO, hyperglycinemia, lipoic acid, LIPT2, metabolic flux, pyruvate dehydrogenase, α-oxoglutarate dehydrogenase.

  • C. H. He, D. S. Black, C. M. Allan, B. Meunier, S. Rahman, et C. F. Clarke, « Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome », Frontiers in Physiology, vol. 8, p. 463, 2017.
    Résumé : Coq9 is required for the stability of a mitochondrial multi-subunit complex, termed the CoQ-synthome, and the deamination step of Q intermediates that derive from para-aminobenzoic acid (pABA) in yeast. In human, mutations in the COQ9 gene cause neonatal-onset primary Q10 deficiency. In this study, we determined whether expression of human COQ9 could complement yeast coq9 point or null mutants. We found that expression of human COQ9 rescues the growth of the temperature-sensitive yeast mutant, coq9-ts19, on a non-fermentable carbon source and increases the content of Q6, by enhancing Q biosynthesis from 4-hydroxybenzoic acid (4HB). To study the mechanism for the rescue by human COQ9, we determined the steady-state levels of yeast Coq polypeptides in the mitochondria of the temperature-sensitive yeast coq9 mutant expressing human COQ9. We show that the expression of human COQ9 significantly increased steady-state levels of yeast Coq4, Coq6, Coq7, and Coq9 at permissive temperature. Human COQ9 polypeptide levels persisted at non-permissive temperature. A small amount of the human COQ9 co-purified with tagged Coq6, Coq6-CNAP, indicating that human COQ9 interacts with the yeast Q-biosynthetic complex. These findings suggest that human COQ9 rescues the yeast coq9 temperature-sensitive mutant by stabilizing the CoQ-synthome and increasing Q biosynthesis from 4HB. This finding provides a powerful approach to studying the function of human COQ9 using yeast as a model.
    Mots-clés : BIOCELL, BIOMIT, coenzyme Q, human homolog, Immunoprecipitation, mitochondrial metabolism, Saccharomyces cerevisiae, temperature-sensitive mutant.

  • C. Jenzer et R. Legouis, « Les multiples facettes de l’autophagie au cours du développement », médecine/sciences, vol. 33, nᵒ 3, p. 238-245, 2017.

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