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1. The fate of mitochondria during platelet activation

Author

Grichine, Alexei, Jacob, Shancy, Eckly, Anita, Villaret, Joran, Joubert, Clotilde, Appaix, Florence, Pezet, Mylène, Ribba, Anne-Sophie, Denarier, Eric, Mazzega, Jacques, Rinckel, Jean-Yves, Lafanechère, Laurence, Elena-Herrmann, Bénédicte, Rowley, Jesse W., and Sadoul, Karin

Published
2023
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4. Short- and long-term efficacy of electroconvulsive stimulation in animal models of depression: The essential role of neuronal survival

Author

Jonckheere, Julie, Deloulme, Jean-Christophe, Dall’Igna, Gaëlle, Chauliac, Nicolas, Pelluet, Albane, Nguon, Anne-Sophie, Lentini, Celia, Brocard, Jacques, Denarier, Eric, Brugière, Sabine, Couté, Yohann, Heinrich, Christophe, Porcher, Christophe, Holtzmann, Jérôme, Andrieux, Annie, Suaud-Chagny, Marie-Françoise, and Gory-Fauré, Sylvie

Published
2018
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5. Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation

Author

Aillaud, Chrystelle, Bosc, Christophe, Peris, Leticia, Bosson, Anouk, Heemeryck, Pierre, Van Dijk, Juliette, Le Friec, Julien, Boulan, Benoit, Vossier, Frédérique, Sanman, Laura E., Syed, Salahuddin, Amara, Neri, Couté, Yohann, Lafanechère, Laurence, Denarier, Eric, Delphin, Christian, Pelletier, Laurent, Humbert, Sandrine, Bogyo, Matthew, Andrieux, Annie, Rogowski, Krzysztof, and Moutin, Marie-Jo

Published
2017

8. VASH1–SVBP and VASH2–SVBP generate different detyrosination profiles on microtubules

Author

Ramirez-Rios, Sacnicte, primary, Choi, Sung Ryul, additional, Sanyal, Chadni, additional, Blum, Thorsten B., additional, Bosc, Christophe, additional, Krichen, Fatma, additional, Denarier, Eric, additional, Soleilhac, Jean-Marc, additional, Blot, Béatrice, additional, Janke, Carsten, additional, Stoppin-Mellet, Virginie, additional, Magiera, Maria M., additional, Arnal, Isabelle, additional, Steinmetz, Michel O., additional, and Moutin, Marie-Jo, additional

Published
2022
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11. A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines

Author

Peris, Leticia, Bisbal, Mariano, Martinez-Hernandez, José, Saoudi, Yasmina, Jonckheere, Julie, Rolland, Marta, Sebastien, Muriel, Brocard, Jacques, Denarier, Eric, Bosc, Christophe, Guerin, Christophe, Gory-Fauré, Sylvie, Deloulme, Jean Christophe, Lanté, Fabien, Arnal, Isabelle, Buisson, Alain, Goldberg, Yves, Blanchoin, Laurent, Delphin, Christian, and Andrieux, Annie

Published
2018
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13. Alix is required for activity-dependent bulk endocytosis at brain synapses

Author

Laporte, Marine H., primary, Chi, Kwang Il, additional, Caudal, Laura C., additional, Zhao, Na, additional, Schwarz, Yvonne, additional, Rolland, Marta, additional, Martinez-Hernandez, José, additional, Martineau, Magalie, additional, Chatellard, Christine, additional, Denarier, Eric, additional, Mercier, Vincent, additional, Lemaître, Florent, additional, Blot, Béatrice, additional, Moutaux, Eve, additional, Cazorla, Maxime, additional, Perrais, David, additional, Lanté, Fabien, additional, Bruns, Dieter, additional, Fraboulet, Sandrine, additional, Hemming, Fiona J., additional, Kirchhoff, Frank, additional, and Sadoul, Rémy, additional

Published
2022
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15. CRMP4-mediated fornix development involves Semaphorin-3E signaling pathway

Author

Boulan, Benoît, primary, Ravanello, Charlotte, primary, Peyrel, Amandine, additional, Bosc, Christophe, additional, Delphin, Christian, additional, Appaix, Florence, additional, Denarier, Eric, additional, Kraut, Alexandra, additional, Jacquier-Sarlin, Muriel, additional, Fournier, Alyson, additional, Andrieux, Annie, additional, Gory-Fauré, Sylvie, additional, and Deloulme, Jean-Christophe, additional

Published
2021
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16. Author response: CRMP4-mediated fornix development involves Semaphorin-3E signaling pathway

Author

Boulan, Benoît, primary, Ravanello, Charlotte, primary, Peyrel, Amandine, additional, Bosc, Christophe, additional, Delphin, Christian, additional, Appaix, Florence, additional, Denarier, Eric, additional, Kraut, Alexandra, additional, Jaquier-Sarlin, Muriel, additional, Fournier, Alyson, additional, Andrieux, Annie, additional, Gory-Fauré, Sylvie, additional, and Deloulme, Jean-Christophe, additional

Published
2021
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17. Pyr1-Mediated Pharmacological Inhibition of LIM Kinase Restores Synaptic Plasticity and Normal Behavior in a Mouse Model of Schizophrenia

Author

Gory-Fauré, Sylvie, Powell, Rebecca, Jonckheere, Julie, Lanté, Fabien, Denarier, Eric, Peris, Leticia, Nguyen, Chi Hung, Buisson, Alain, Lafanechère, Laurence, Andrieux, Annie, Lafanechère, Laurence, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)

Subjects
Pharmacology, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, cytoskeleton, [SDV] Life Sciences [q-bio], cognitive abilities, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MAP6, therapeutics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Pharmacology (medical), LIM kinase, actin, microtubule
Abstract

International audience; The search for effective treatments for neuropsychiatric disorders is ongoing, with progress being made as brain structure and neuronal function become clearer. The central roles played by microtubules (MT) and actin in synaptic transmission and plasticity suggest that the cytoskeleton and its modulators could be relevant targets for the development of new molecules to treat psychiatric diseases. In this context, LIM Kinase - which regulates both the actin and MT cytoskeleton especially in dendritic spines, the post-synaptic compartment of the synapse - might be a good target. In this study, we analyzed the consequences of blocking LIMK1 pharmacologically using Pyr1. We investigated synaptic plasticity defects and behavioral disorders in MAP6 KO mice, an animal model useful for the study of psychiatric disorders, particularly schizophrenia. Our results show that Pyr1 can modulate MT dynamics in neurons. In MAP6 KO mice, chronic LIMK inhibition by long-term treatment with Pyr1 can restore normal dendritic spine density and also improves long-term potentiation, both of which are altered in these mice. Pyr1 treatment improved synaptic plasticity, and also reduced social withdrawal and depressive/anxiety-like behavior in MAP6 KO mice. Overall, the results of this study validate the hypothesis that modulation of LIMK activity could represent a new therapeutic strategy for neuropsychiatric diseases.

Published
2021
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19. Two Antagonistic Microtubule Targeting Drugs Act Synergistically to Kill Cancer Cells

Author

Peronne, Lauralie, Denarier, Eric, Rai, Ankit, Prudent, Renaud, Vernet, Audrey, Suzanne, Peggy, Ramirez-Rios, Sacnicté, Michallet, Sophie, Guidetti, Mélanie, Vollaire, Julien, Lucena-Agell, Daniel, Ribba, Anne-Sophie, Josserand, Véronique, Coll, Jean-Luc, Dallemagne, Patrick, Díaz, J Fernando, Oliva, María Ángela, Sadoul, Karin, Akhmanova, Anna, Andrieux, Annie, Lafanechère, Laurence, Sub Cell Biology, and Celbiologie

Subjects
microtubules, paclitaxel, drug synergy, carbazole, cancer therapy
Abstract

Paclitaxel is a microtubule stabilizing agent and a successful drug for cancer chemotherapy inducing, however, adverse effects. To reduce the effective dose of paclitaxel, we searched for pharmaceutics which could potentiate its therapeutic effect. We screened a chemical library and selected Carba1, a carbazole, which exerts synergistic cytotoxic effects on tumor cells grown in vitro, when co-administrated with a low dose of paclitaxel. Carba1 targets the colchicine binding-site of tubulin and is a microtubule-destabilizing agent. Catastrophe induction by Carba1 promotes paclitaxel binding to microtubule ends, providing a mechanistic explanation of the observed synergy. The synergistic effect of Carba1 with paclitaxel on tumor cell viability was also observed in vivo in xenografted mice. Thus, a new mechanism favoring paclitaxel binding to dynamic microtubules can be transposed to in vivo mouse cancer treatments, paving the way for new therapeutic strategies combining low doses of microtubule targeting agents with opposite mechanisms of action.

Published
2020

20. Two Antagonistic Microtubule Targeting Drugs Act Synergistically to Kill Cancer Cells

Author

Sub Cell Biology, Celbiologie, Peronne, Lauralie, Denarier, Eric, Rai, Ankit, Prudent, Renaud, Vernet, Audrey, Suzanne, Peggy, Ramirez-Rios, Sacnicté, Michallet, Sophie, Guidetti, Mélanie, Vollaire, Julien, Lucena-Agell, Daniel, Ribba, Anne-Sophie, Josserand, Véronique, Coll, Jean-Luc, Dallemagne, Patrick, Díaz, J Fernando, Oliva, María Ángela, Sadoul, Karin, Akhmanova, Anna, Andrieux, Annie, Lafanechère, Laurence, Sub Cell Biology, Celbiologie, Peronne, Lauralie, Denarier, Eric, Rai, Ankit, Prudent, Renaud, Vernet, Audrey, Suzanne, Peggy, Ramirez-Rios, Sacnicté, Michallet, Sophie, Guidetti, Mélanie, Vollaire, Julien, Lucena-Agell, Daniel, Ribba, Anne-Sophie, Josserand, Véronique, Coll, Jean-Luc, Dallemagne, Patrick, Díaz, J Fernando, Oliva, María Ángela, Sadoul, Karin, Akhmanova, Anna, Andrieux, Annie, and Lafanechère, Laurence

Published
2020

21. Two antagonistic microtubule targeting drugs act synergistically to kill cancer cells

Author

Université Grenoble Alpes, Institut National de la Santé et de la Recherche Médicale (France), Centre National de la Recherche Scientifique (France), Institut National du Cancer (France), Fondation ARC pour la Recherche sur le Cancer, European Commission, Ministerio de Economía y Competitividad (España), Netherlands Organization for Scientific Research, Peronne, Lauralie, Denarier, Eric, Rai, Ankit, Prudent, Renaud, Vernet, Audrey, Suzanne, Peggy, Ramírez-Ríos, Sacnicte, Michallet, Sophie, Guidetti, Mélanie, Vollaire, Julien, Lucena-Agell, Daniel, Ribba, Anne-Sophie, Josserand, Véronique, Coll, Jean-Luc, Dallemagne, Patrick, Díaz, José Fernando, Oliva, María A., Sadoul, Karin, Akhmanova, Anna, Andrieux, Annie, Lafanechère, Laurence, Université Grenoble Alpes, Institut National de la Santé et de la Recherche Médicale (France), Centre National de la Recherche Scientifique (France), Institut National du Cancer (France), Fondation ARC pour la Recherche sur le Cancer, European Commission, Ministerio de Economía y Competitividad (España), Netherlands Organization for Scientific Research, Peronne, Lauralie, Denarier, Eric, Rai, Ankit, Prudent, Renaud, Vernet, Audrey, Suzanne, Peggy, Ramírez-Ríos, Sacnicte, Michallet, Sophie, Guidetti, Mélanie, Vollaire, Julien, Lucena-Agell, Daniel, Ribba, Anne-Sophie, Josserand, Véronique, Coll, Jean-Luc, Dallemagne, Patrick, Díaz, José Fernando, Oliva, María A., Sadoul, Karin, Akhmanova, Anna, Andrieux, Annie, and Lafanechère, Laurence

Abstract

Paclitaxel is a microtubule stabilizing agent and a successful drug for cancer chemotherapy inducing, however, adverse effects. To reduce the effective dose of paclitaxel, we searched for pharmaceutics which could potentiate its therapeutic effect. We screened a chemical library and selected Carba1, a carbazole, which exerts synergistic cytotoxic effects on tumor cells grown in vitro, when co-administrated with a low dose of paclitaxel. Carba1 targets the colchicine binding-site of tubulin and is a microtubule-destabilizing agent. Catastrophe induction by Carba1 promotes paclitaxel binding to microtubule ends, providing a mechanistic explanation of the observed synergy. The synergistic effect of Carba1 with paclitaxel on tumor cell viability was also observed in vivo in xenografted mice. Thus, a new mechanism favoring paclitaxel binding to dynamic microtubules can be transposed to in vivo mouse cancer treatments, paving the way for new therapeutic strategies combining low doses of microtubule targeting agents with opposite mechanisms of action.

Published
2020

22. ALG-2 interacting protein-X (Alix) is required for activity-dependent bulk endocytosis at brain synapses

Author

Laporte, Marine H., primary, Chi, Kwang Il, additional, Caudal, Laura C., additional, Zhao, Na, additional, Rolland, Marta, additional, Martinez-Hernandez, José, additional, Martineau, Magalie, additional, Chatellard, Christine, additional, Denarier, Eric, additional, Mercier, Vincent, additional, Lemaître, Florent, additional, Blot, Béatrice, additional, Moutaux, Eve, additional, Cazorla, Maxime, additional, Perrais, David, additional, Lanté, Fabien, additional, Fraboulet, Sandrine, additional, Hemming, Fiona J., additional, Kirchhoff, Frank, additional, and Sadoul, Rémy, additional

Published
2020
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24. Presynaptic APP levels and synaptic homeostasis are regulated by Akt phosphorylation of huntingtin

Author

Bruyère, Julie, primary, Abada, Yah-Se, additional, Vitet, Hélène, additional, Fontaine, Gaëlle, additional, Deloulme, Jean-Christophe, additional, Cès, Aurélia, additional, Denarier, Eric, additional, Pernet-Gallay, Karin, additional, Andrieux, Annie, additional, Humbert, Sandrine, additional, Potier, Marie-Claude, additional, Delatour, Benoît, additional, and Saudou, Frédéric, additional

Published
2020
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25. Author response: Presynaptic APP levels and synaptic homeostasis are regulated by Akt phosphorylation of huntingtin

Author

Bruyère, Julie, primary, Abada, Yah-Se, additional, Vitet, Hélène, additional, Fontaine, Gaëlle, additional, Deloulme, Jean-Christophe, additional, Cès, Aurélia, additional, Denarier, Eric, additional, Pernet-Gallay, Karin, additional, Andrieux, Annie, additional, Humbert, Sandrine, additional, Potier, Marie-Claude, additional, Delatour, Benoît, additional, and Saudou, Frédéric, additional

Published
2020
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26. MAP6 is an intraluminal protein that induces neuronal microtubules to coil

Author

Cuveillier, Camille, primary, Delaroche, Julie, additional, Seggio, Maxime, additional, Gory-Fauré, Sylvie, additional, Bosc, Christophe, additional, Denarier, Eric, additional, Bacia, Maria, additional, Schoehn, Guy, additional, Mohrbach, Hervé, additional, Kulić, Igor, additional, Andrieux, Annie, additional, Arnal, Isabelle, additional, and Delphin, Christian, additional

Published
2020
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27. Two antagonistic microtubule targeting drugs act synergistically to kill cancer cells

Author

Peronne, Lauralie, primary, Denarier, Eric, additional, Rai, Ankit, additional, Prudent, Renaud, additional, Vernet, Audrey, additional, Suzanne, Peggy, additional, Ramirez-Rios, Sacnicté, additional, Michallet, Sophie, additional, Guidetti, Mélanie, additional, Vollaire, Julien, additional, Lucena-Agell, Daniel, additional, Ribba, Anne-Sophie, additional, Josserand, Véronique, additional, Coll, Jean-Luc, additional, Dallemagne, Patrick, additional, Díaz, J. Fernando, additional, Oliva, María Ángela, additional, Sadoul, Karin, additional, Akhmanova, Anna, additional, Andrieux, Annie, additional, and Lafanechère, Laurence, additional

Published
2020
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28. MAP6 is an intraluminal protein that induces neuronal microtubules to coil

Author

Cuveillier, Camille, Delaroche, Julie, Seggio, Maxime, Gory-Fauré, Sylvie, Bosc, Christophe, Denarier, Eric, Bacia, Maria, Schoehn, Guy, Mohrbach, Hervé, Kulić, Igor, Andrieux, Annie, Arnal, Isabelle, Delphin, Christian, Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Laboratoire de Physique et Chimie Théoriques (LPCT), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Sadron (ICS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), EM platform ISBG, platforms of the Grenoble Instruct-ERIC centre (ISBG, UMS 3518 CNRS-CEA-UGA-EMBL), Grenoble Partnership for Structural Biology (PSB), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-17-CE11-0026,MAMAs,Coordination des microtubules et de l'actine par les MAPs structurales(2017), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Thomas, Frank, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, and CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID

Subjects
Neurons, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV]Life Sciences [q-bio], SciAdv r-articles, Cell Biology, Microtubules, Models, Biological, Mice, Protein Transport, nervous system, Developmental Neuroscience, Neurites, Animals, Microtubule-Associated Proteins, Research Articles, ComputingMilieux_MISCELLANEOUS, Research Article, Protein Binding
Abstract

MAP6 enters the lumen and induces coiling in a previously unidentified class of neuronal microtubules., Neuronal activities depend heavily on microtubules, which shape neuronal processes and transport myriad molecules within them. Although constantly remodeled through growth and shrinkage events, neuronal microtubules must be sufficiently stable to maintain nervous system wiring. This stability is somehow maintained by various microtubule-associated proteins (MAPs), but little is known about how these proteins work. Here, we show that MAP6, previously known to confer cold stability to microtubules, promotes growth. More unexpectedly, MAP6 localizes in the lumen of microtubules, induces the microtubules to coil into a left-handed helix, and forms apertures in the lattice, likely to relieve mechanical stress. These features have not been seen in microtubules before and could play roles in maintaining axonal width or providing flexibility in the face of compressive forces during development.

Published
2019
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29. A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning

Author

Denarier, Eric, Brousse, Carine, Sissoko, Abdoulaye, Andrieux, Annie, Boscheron, Cécile, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Physiopathologie du Cytosquelette (GPC), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Transfusion Sanguine [Paris] (INTS), Université Paris Descartes - Paris 5 (UPD5), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Thomas, Frank

Subjects
TUBB2B, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], QH301-705.5, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Science, Microtubule, macromolecular substances, Biology (General), Yeast, Spindle positioning, Research Article, EB1
Abstract

Malformations of the human cerebral cortex can be caused by mutations in tubulins that associate to compose microtubules. Cerebral cortical folding relies on neuronal migration and on progenitor proliferation partly dictated by microtubule-dependent mitotic spindle positioning. A single amino acid change, F265L, in the conserved TUBB2B β-tubulin gene has been identified in patients with abnormal cortex formation. A caveat for studying this mutation in mammalian cells is that nine genes encode β-tubulin in human. Here, we generate a yeast strain expressing F265L tubulin mutant as the sole source of β-tubulin. The F265L mutation does not preclude expression of a stable β-tubulin protein which is incorporated into microtubules. However, impaired cell growth was observed at high temperatures along with altered microtubule dynamics and stability. In addition, F265L mutation produces a highly specific mitotic spindle positioning defect related to Bim1 (yeast EB1) dysfunction. Indeed, F265L cells display an abnormal Bim1 recruitment profile at microtubule plus-ends. These results indicate that the F265L β-tubulin mutation affects microtubule plus-end complexes known to be important for microtubule dynamics and for microtubule function during mitotic spindle positioning., Summary: Patients with intellectual disabilities carry a F265L mutation in TUBB2B β-tubulin gene. Yeast used as a cellular model reveals spindle mis-positioning associated with reduced yeast EB1 affinity for microtubule plus-ends.

Published
2019
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32. A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines

Author

Bioquímica y biología molecular, Biokimika eta biologia molekularra, Peris, Leticia, Bisbal, Mariano, Martínez Hernández, José, Saoudi, Yasmina, Jonckheere, Julie, Rolland, Marta, Sebastien, Muriel, Brocard, Jacques, Denarier, Eric, Bosc, Christophe, Guerin, Christophe, Gory-Fauré, Sylvie, Deloulme, Jean Christophe, Lanté, Fabien, Arnal, Isabelle, Buisson, Alain, Goldberg, Yves, Blanchoin, Laurent, Bioquímica y biología molecular, Biokimika eta biologia molekularra, Peris, Leticia, Bisbal, Mariano, Martínez Hernández, José, Saoudi, Yasmina, Jonckheere, Julie, Rolland, Marta, Sebastien, Muriel, Brocard, Jacques, Denarier, Eric, Bosc, Christophe, Guerin, Christophe, Gory-Fauré, Sylvie, Deloulme, Jean Christophe, Lanté, Fabien, Arnal, Isabelle, Buisson, Alain, Goldberg, Yves, and Blanchoin, Laurent

Abstract

Emerging evidence indicates that microtubule-associated proteins (MAPs) are implicated in synaptic function; in particular, mice deficient for MAP6 exhibit striking deficits in plasticity and cognition. How MAP6 connects to plasticity mechanisms is unclear. Here, we address the possible role of this protein in dendritic spines. We find that in MAP6-deficient cortical and hippocampal neurons, maintenance of mature spines is impaired, and can be restored by expressing a stretch of the MAP6 sequence called Mc modules. Mc modules directly bind actin filaments and mediate activity-dependent stabilisation of F-actin in dendritic spines, a key event of synaptic plasticity. In vitro, Mc modules enhance actin filament nucleation and promote the formation of stable, highly ordered filament bundles. Activity-induced phosphorylation of MAP6 likely controls its transfer to the spine cytoskeleton. These results provide a molecular explanation for the role of MAP6 in cognition, enlightening the connection between cytoskeletal dysfunction, synaptic impairment and neuropsychiatric illnesses.

Published
2018

33. MAP6 interacts with Tctex1 and Cav 2.2/N-type calcium channels to regulate calcium signalling in neurons

Author

Brocard, Jacques, Dufour, Fabrice, Gory‐Fauré, Sylvie, Arnoult, Christophe, Bosc, Christophe, Denarier, Eric, Peris, Leticia, Saoudi, Yasmina, De Waard, Michel, Andrieux, Annie, Physiopathologie du Cytosquelette, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), INSERM U836, équipe 1, Physiopathologie du cytosquelette, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm, U1216, Grenoble, France., Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Groupe Physiopathologie du Cytosquelette (GPC), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
Mice, Knockout, Neurons, vesicles, Binding Sites, yeast two-hybrid, hippocampal neurons, [SDV]Life Sciences [q-bio], Dyneins, in vitro interactions, Molecular and Synaptic Mechanisms, plasma membrane, Hippocampus, microtubules, Mice, Calcium Channels, N-Type, Animals, Female, Calcium Signaling, yeast two‐hybrid, Microtubule-Associated Proteins, Cells, Cultured, Protein Binding
Abstract

International audience; MAP6 proteins were first described as microtubule-stabilizing agents, whose properties were thought to be essential for neuronal development and maintenance of complex neuronal networks. However, deletion of all MAP6 isoforms in MAP6 KO mice does not lead to dramatic morphological aberrations of the brain but rather to alterations in multiple neurotransmissions and severe behavioural impairments. A search for protein partners of MAP6 proteins identified Tctex1 - a dynein light chain with multiple non-microtubule-related functions. The involvement of Tctex1 in calcium signalling led to investigate it in MAP6 KO neurons. In this study, we show that functional Cav 2.2/N-type calcium channels are deficient in MAP6 KO neurons, due to improper location. We also show that MAP6 proteins interact directly with both Tctex1 and the C-terminus of Cav 2.2/N-type calcium channels. A balance of these two interactions seems to be crucial for MAP6 to modulate calcium signalling in neurons.

Published
2017
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34. 3D imaging of the brain morphology and connectivity defects in a model of psychiatric disorders: MAP6-KO mice

Author

Gimenez, Ulysse, Boulan, Benoit, Mauconduit, Franck, Taurel, Fanny, Leclercq, Maxime, Denarier, Eric, Brocard, Jacques, Gory-Fauré, Sylvie, Andrieux, Annie, Lahrech, Hana, and Deloulme, Jean Christophe

Subjects
Male, Mice, Knockout, Brain Mapping, Mental Disorders, lcsh:R, lcsh:Medicine, Brain, Magnetic Resonance Imaging, Article, Disease Models, Animal, Mice, Imaging, Three-Dimensional, nervous system, Microscopy, Fluorescence, Neural Pathways, Image Processing, Computer-Assisted, Animals, lcsh:Q, Female, lcsh:Science, Microtubule-Associated Proteins
Abstract

In the central nervous system, microtubule-associated protein 6 (MAP6) is expressed at high levels and is crucial for cognitive abilities. The large spectrum of social and cognitive impairments observed in MAP6-KO mice are reminiscent of the symptoms observed in psychiatric diseases, such as schizophrenia, and respond positively to long-term treatment with antipsychotics. MAP6-KO mice have therefore been proposed to be a useful animal model for these diseases. Here, we explored the brain anatomy in MAP6-KO mice using high spatial resolution 3D MRI, including a volumetric T1w method to image brain structures, and Diffusion Tensor Imaging (DTI) for white matter fiber tractography. 3D DTI imaging of neuronal tracts was validated by comparing results to optical images of cleared brains. Changes to brain architecture included reduced volume of the cerebellum and the thalamus and altered size, integrity and spatial orientation of some neuronal tracks such as the anterior commissure, the mammillary tract, the corpus callosum, the corticospinal tract, the fasciculus retroflexus and the fornix. Our results provide information on the neuroanatomical defects behind the neurological phenotype displayed in the MAP6-KO mice model and especially highlight a severe damage of the corticospinal tract with defasciculation at the location of the pontine nuclei.

Published
2017

35. Phase from defocus

Author

Hervé, Lionel, primary, Mandula, Ondrej, primary, Allier, Cédric, primary, Denarier, Eric, primary, Fourest-Lieuvin, Anne, primary, Morales, Sophie, primary, Vinit, Angelique, primary, and Gory-Faure, Sylvie, primary

Published
2018
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36. Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation- dependent mechanism

Author

Ramirez-Rios, Sacnicte, Denarier, Eric, Prezel, Elea, Vinit, Angélique, Stoppin-Mellet, Virginie, Devred, François, Barbier, Pascale, Peyrot, Vincent, Sayas, Carmen Laura, Avila, Jesús, Peris, Leticia, Andrieux, Annie, Serre, Laurence, Fourest-Lieuvin, Anne, Arnal, Isabelle, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratory of Developmental Biology, McGill University, INSERM U836, équipe 1, Physiopathologie du cytosquelette, Groupe Physiopathologie du Cytosquelette (GPC), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de La Laguna [Tenerife - SP] (ULL), CBM Severo Ochoa, Universidad Autonoma de Madrid (UAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des Protéines Membranaires (LPM), Institut de biologie structurale (IBS - UMR 5075), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada], Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Grenoble Institut des Neurosciences (GIN), Universidad Autónoma de Madrid (UAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
phosphorylation, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, mental disorders, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, tau, EB1, microtubule
Abstract

International audience; Proper regulation of microtubule dynamics is essential for cell functions and involves various microtubule-associated proteins (MAPs). Among them, end-binding proteins (EBs) accumulate at microtubule plus ends, whereas structural MAPs bind along the microtu-bule lattice. Recent data indicate that the structural MAP tau modulates EB subcellular local-ization in neurons. However, the molecular determinants of EB/tau interaction remain unknown , as is the effect of this interplay on microtubule dynamics. Here we investigate the mechanisms governing EB/tau interaction in cell-free systems and cellular models. We find that tau inhibits EB tracking at microtubule ends. Tau and EBs form a complex via the C-terminal region of EBs and the microtubule-binding sites of tau. These two domains are required for the inhibitory activity of tau on EB localization to microtubule ends. Moreover, the phos-phomimetic mutation S262E within tau microtubule-binding sites impairs EB/tau interaction and prevents the inhibitory effect of tau on EB comets. We further show that microtubule dynamic parameters vary, depending on the combined activities of EBs and tau proteins. Overall our results demonstrate that tau directly antagonizes EB function through a phos-phorylation-dependent mechanism. This study highlights a novel role for tau in EB regulation, which might be impaired in neurodegenerative disorders.

Published
2016
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37. Dynamics of Triad Organization

Author

Sébastien, Muriel, primary, Teyssier, Perrine, additional, Brocard, Julie, additional, Denarier, Eric, additional, Marty, Isabelle, additional, and Fauré, Julien, additional

Published
2017
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38. Tau co-organizes dynamic microtubule and actin networks

Author

Elie, Auréliane, Prezel, Elea, Guérin, Christophe, Denarier, Eric, Ramirez-Rios, Sacnicte, Serre, Laurence, Andrieux, Annie, Fourest-Lieuvin, Anne, Blanchoin, Laurent, Arnal, Isabelle, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Groupe Physiopathologie du Cytosquelette (GPC), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pre-doctoral fellowships from the Région Rhône-Alpes (Program 'Cible 2011')- Fondation pour la Recherche Médicale (FDT20140930826)- Post-doctoral fellowships from the Université Joseph Fourier (Grenoble), ANR-11-MALZ-0001,MAALAD,Perturbation du cytosquelette dans la maladie d'Alzheimer : étude cellulaire et moléculaire(2011), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), [GIN] Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Martin-Laffon, Jacqueline, and Maladie d'Alzheimer et Maladies Apparentées - Perturbation du cytosquelette dans la maladie d'Alzheimer : étude cellulaire et moléculaire - - MAALAD2011 - ANR-11-MALZ-0001 - MALZ - VALID

Subjects
Protein Conformation, protéine associee, Microtubule associated protein, tau Proteins, macromolecular substances, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, polymérisation, Microtubules, Nervous System, Article, Polymerization, actine, Motion, cytosquelette, neurone, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], système nerveux, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cytoskeleton, Neurons, Binding Sites, Neurosciences, neurons, cytoskeleton, microtubule/actin crosslinking, polymerization, microtubule associated protein, nervous system, tau protein, Tau Protein, Actins, Actin Cytoskeleton, Cross-Linking Reagents, Neurons and Cognition, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], microtubule, Protein Binding
Abstract

International audience; The crosstalk between microtubules and actin is essential for cellular functions. However, mechanisms underlying the microtubule-actin organization by cross-linkers remain largely unexplored. Here, we report that tau, a neuronal microtubule-associated protein, binds to microtubules and actin simultaneously, promoting in vitro co-organization and coupled growth of both networks. By developing an original assay to visualize concomitant microtubule and actin assembly, we show that tau can induce guided polymerization of actin filaments along microtubule tracks and growth of single microtubules along actin filament bundles. Importantly, tau mediates microtubule-actin co-alignment without changing polymer growth properties. Mutagenesis studies further reveal that at least two of the four tau repeated motifs, primarily identified as tubulin-binding sites, are required to connect microtubules and actin. Tau thus represents a molecular linker between microtubule and actin networks, enabling a coordination of the two cytoskeletons that might be essential in various neuronal contexts.

Published
2015

39. Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice.

Author

Pagnamenta, Alistair T, Heemeryck, Pierre, Martin, Hilary C, Bosc, Christophe, Peris, Leticia, Uszynski, Ivy, Gory-Fauré, Sylvie, Couly, Simon, Deshpande, Charu, Siddiqui, Ata, Elmonairy, Alaa A, Consortium, WGS500, Consortium, Genomics England Research, Jayawant, Sandeep, Murthy, Sarada, Walker, Ian, Loong, Lucy, Bauer, Peter, Vossier, Frédérique, and Denarier, Eric

Published
2019
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40. Evidence for new C-terminally truncated variants of α- and β-tubulins

Author

Aillaud, Chrystelle, primary, Bosc, Christophe, additional, Saoudi, Yasmina, additional, Denarier, Eric, additional, Peris, Leticia, additional, Sago, Laila, additional, Taulet, Nicolas, additional, Cieren, Adeline, additional, Tort, Olivia, additional, Magiera, Maria M., additional, Janke, Carsten, additional, Redeker, Virginie, additional, Andrieux, Annie, additional, and Moutin, Marie-Jo, additional

Published
2016
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42. Phase from defocus.

Author

Mandula, Ondrej, Allier, Cédric, Hervé, Lionel, Denarier, Eric, Fourest-Lieuvin, Anne, Gory-Fauré, Sylvie, Vinit, Angélique, and Morales, Sophie

Published
2017
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44. Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth

Author

Deloulme, Jean-Christophe, primary, Gory-Fauré, Sylvie, additional, Mauconduit, Franck, additional, Chauvet, Sophie, additional, Jonckheere, Julie, additional, Boulan, Benoit, additional, Mire, Erik, additional, Xue, Jing, additional, Jany, Marion, additional, Maucler, Caroline, additional, Deparis, Agathe A., additional, Montigon, Olivier, additional, Daoust, Alexia, additional, Barbier, Emmanuel L., additional, Bosc, Christophe, additional, Deglon, Nicole, additional, Brocard, Jacques, additional, Denarier, Eric, additional, Le Brun, Isabelle, additional, Pernet-Gallay, Karin, additional, Vilgrain, Isabelle, additional, Robinson, Phillip J., additional, Lahrech, Hana, additional, Mann, Fanny, additional, and Andrieux, Annie, additional

Published
2015
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45. MAP6 interacts with Tctex1 and Cav2.2/N-type calcium channels to regulate calcium signalling in neurons.

Author

Brocard, Jacques, Dufour, Fabrice, Gory‐Fauré, Sylvie, Arnoult, Christophe, Bosc, Christophe, Denarier, Eric, Peris, Leticia, Saoudi, Yasmina, De Waard, Michel, and Andrieux, Annie

Subjects
HIPPOCAMPUS (Brain), NEURONS, MICROTUBULES, CELL membranes, SYNAPTIC vesicles
Abstract

MAP6 proteins were first described as microtubule-stabilizing agents, whose properties were thought to be essential for neuronal development and maintenance of complex neuronal networks. However, deletion of all MAP6 isoforms in MAP6 KO mice does not lead to dramatic morphological aberrations of the brain but rather to alterations in multiple neurotransmissions and severe behavioural impairments. A search for protein partners of MAP6 proteins identified Tctex1 - a dynein light chain with multiple non-microtubule-related functions. The involvement of Tctex1 in calcium signalling led to investigate it in MAP6 KO neurons. In this study, we show that functional Cav2.2/N-type calcium channels are deficient in MAP6 KO neurons, due to improper location. We also show that MAP6 proteins interact directly with both Tctex1 and the C-terminus of Cav2.2/N-type calcium channels. A balance of these two interactions seems to be crucial for MAP6 to modulate calcium signalling in neurons. [ABSTRACT FROM AUTHOR]

Published
2017
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46. Non-Microtubular Localizations of Microtubule-Associated Protein 6 (MAP6)

Author

Gory-Fauré, Sylvie, primary, Windscheid, Vanessa, additional, Brocard, Jacques, additional, Montessuit, Sylvie, additional, Tsutsumi, Ryouhei, additional, Denarier, Eric, additional, Fukata, Yuko, additional, Bosc, Christophe, additional, Delaroche, Julie, additional, Collomb, Nora, additional, Fukata, Masaki, additional, Martinou, Jean-Claude, additional, Pernet-Gallay, Karin, additional, and Andrieux, Annie, additional

Published
2014
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47. Phase from defocus

Author

Popescu, Gabriel, Park, YongKeun, Mandula, Ondrej, Allier, Cédric, Hervé, Lionel, Denarier, Eric, Fourest-Lieuvin, Anne, Gory-Fauré, Sylvie, Vinit, Angélique, and Morales, Sophie

Published
2018
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48. A role for the yeast CLIP170 ortholog, the plus-end-tracking protein Bik1, and the Rho1 GTPase in Snc1 trafficking.

Author

Boscheron, Ce'cile, Caudron, Fabrice, Loeillet, Sophie, Peloso, Charlotte, Mugnier, Marine, Kurzawa, Laetitia, Nicolas, Alain, Denarier, Eric, Aubry, Laurence, and Andrieux, Annie

Subjects
MICROTUBULES, RHO factor, C-terminal residues, ENDOCYTOSIS, AMINO acids
Abstract

The diversity of microtubule functions is dependent on the status of tubulin C-termini. To address the physiological role of the C-terminal aromatic residue of a-tubulin, a tub1-Glu yeast strain expressing an a-tubulin devoid of its C-terminal amino acid was used to perform a genome-wide-lethality screen. The identified synthetic lethal genes suggested links with endocytosis and related processes. In the tub1- Glu strain, the routing of the v-SNARE Snc1 was strongly impaired, with a loss of its polarized distribution in the bud, and Abp1, an actin patch or endocytic marker, developed comet-tail structures. Snc1 trafficking required dynamic microtubules but not dynein and kinesin motors. Interestingly, deletion of the microtubule plus-end-tracking protein Bik1 (a CLIP170 ortholog), which is preferentially recruited to the C-terminal residue of a-tubulin, similarly resulted in Snc1 trafficking defects. Finally, constitutively active Rho1 rescued both Bik1 localization at the microtubule plus-ends in tub1-Glu strain and a correct Snc1 trafficking in a Bik1-dependent manner. Our results provide the first evidence for a role of microtubule plus-ends in membrane cargo trafficking in yeast, through Rho1- and Bik1- dependent mechanisms, and highlight the importance of the C-terminal a-tubulin amino acid in this process. [ABSTRACT FROM AUTHOR]

Published
2016
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49. VASH1--SVBP and VASH2--SVBP generate different detyrosination profiles on microtubules.

Author

Ramirez-Rios, Sacnicte, Sung Ryul Choi, Sanyal, Chadni, Blum, Thorsten B., Bosc, Christophe, Krichen, Fatma, Denarier, Eric, Soleilhac, Jean-Marc, Blot, Béatrice, Janke, Carsten, Stoppin-Mellet, Virginie, Magiera, Maria M., Arnal, Isabelle, Steinmetz, Michel O., and Moutin, Marie-Jo

Abstract

The detyrosination/tyrosination cycle of α-tubulin is critical for proper cell functioning. VASH1--SVBP and VASH2--SVBP are ubiquitous enzymes involved in microtubule detyrosination, whose mode of action is little known. Here, we show in reconstituted systems and cells that VASH1--SVBP and VASH2--SVBP drive the global and local detyrosination of microtubules, respectively. We solved the cryo-electron microscopy structure of VASH2--SVBP bound to microtubules, revealing a different microtubule-binding configuration of its central catalytic region compared to VASH1--SVBP. We show that the divergent mode of detyrosination between the two enzymes is correlated with the microtubule-binding properties of their disordered N- and C-terminal regions. Specifically, the N-terminal region is responsible for a significantly longer residence time of VASH2--SVBP on microtubules compared to VASH1--SVBP. We suggest that this VASH region is critical for microtubule detachment and diffusion of VASH--SVBP enzymes on lattices. Our results suggest a mechanism by which VASH1--SVBP and VASH2--SVBP could generate distinct microtubule subpopulations and confined areas of detyrosinated lattices to drive various microtubule-based cellular functions. [ABSTRACT FROM AUTHOR]

Published
2023
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50. A role for the microtubule +end protein Bik1 (CLIP170) and the Rho1 GTPase in Snc1 trafficking

Author

Alain Nicolas, Fabrice Caudron, Cécile Boscheron, Annie Andrieux, Laetitia Kurzawa, Marine Mugnier, Laurence Aubry, Sophie Loeillet, Charlotte Peloso, Eric Denarier, [GIN] Grenoble Institut des Neurosciences, Institut de Biosciences et de Biotechnologies de Grenoble (ex-IRTSV) (BIG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes (UGA), Department of Biology [Zürich, Switzerland], Ecole Polytechnique Fédérale de Zurich, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ARC 7927 grant to AA, and by the INCA 'TetraTips' to AA (PLBIO10-030), ANR Tyr-TIPs (Blan07-2_187328),ANR Tyr-TIPs (Blan07-2_187328), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), ANR-07-BLAN-0045,Tyr-TIPs,Cell regulations at microtubule +ends: shifting from a Darwinist to a deterministic view of microtubule organization and of cell morphogenesis(2007), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Denarier, Eric, and Blanc - Cell regulations at microtubule +ends: shifting from a Darwinist to a deterministic view of microtubule organization and of cell morphogenesis - - Tyr-TIPs2007 - ANR-07-BLAN-0045 - BLANC - VALID

Subjects
0301 basic medicine, Microtubule-associated protein, [SDV]Life Sciences [q-bio], Dynein, Endocytic cycle, Saccharomyces cerevisiae, macromolecular substances, tyrosination, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Microtubules, 03 medical and health sciences, Microtubule, trafficking, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, fungi, +Tips, Cell Biology, biology.organism_classification, Cell biology, Transport protein, [SDV] Life Sciences [q-bio], 030104 developmental biology, Tubulin, biology.protein, Kinesin, Rho1, CLIP170
Abstract

The diversity of microtubule functions is dependent on the status of tubulin C-termini. To address the physiological role of the C-terminal aromatic residue of α-tubulin, a tub1-Glu yeast strain expressing an α-tubulin devoid of its C-terminal amino acid was used to perform a genome-wide-lethality screen. The identified synthetic lethal genes suggested links with endocytosis and related processes. In the tub1-Glu strain, the routing of the v-SNARE Snc1 was strongly impaired, with a loss of its polarized distribution in the bud, and Abp1, an actin patch or endocytic marker, developed comet-tail structures. Snc1 trafficking required dynamic microtubules but not dynein and kinesin motors. Interestingly, deletion of the microtubule plus-end-tracking protein Bik1 (a CLIP170 ortholog), which is preferentially recruited to the C-terminal residue of α-tubulin, similarly resulted in Snc1 trafficking defects. Finally, constitutively active Rho1 rescued both Bik1 localization at the microtubule plus-ends in tub1-Glu strain and a correct Snc1 trafficking in a Bik1-dependent manner. Our results provide the first evidence for a role of microtubule plus-ends in membrane cargo trafficking in yeast, through Rho1- and Bik1-dependent mechanisms, and highlight the importance of the C-terminal α-tubulin amino acid in this process.

Published
2016
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