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6. A Vital Role of Tubulin-Tyrosine-Ligase for Neuronal Organization

Author

Erck, Christian, Peris, Leticia, Andrieux, Annie, Meissirel, Claire, Gruber, Achim D., Vernet, Muriel, Schweitzer, Annie, Saoudi, Yasmina, Pointu, Hervé, Bosc, Christophe, Salin, Paul A., Job, Didier, Wehland, Juergen, and Vale, Ronald D.

Published
2005

8. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

Author

Charlet, Alexandre, Muller, Arnaud H, Laux, Alexis, Kemmel, Véronique, Schweitzer, Annie, Deloulme, Jean-Christophe, Stuber, Denise, Delalande, François, Bianchi, Enrica, Van Dorsselaer, Alain, Aunis, Dominique, Andrieux, Annie, Poisbeau, Pierrick, and Goumon, Yannick

Abstract

Abstract Background- Mice deficient for the stable tubule only peptide (STOP) display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p.) produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg) was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg) was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

Published
2010

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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12. Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease

Author

Martínez-Hernández, José, primary, Parato, Julie, additional, Sharma, Aditi, additional, Soleilhac, Jean-Marc, additional, Qu, Xiaoyi, additional, Tein, Ellen, additional, Sproul, Andrew, additional, Andrieux, Annie, additional, Goldberg, Yves, additional, Moutin, Marie-Jo, additional, Bartolini, Francesca, additional, and Peris, Leticia, additional

Published
2022
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16. Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer’s disease

Author

Peris, Leticia, primary, Parato, Julie, additional, Qu, Xiaoyi, additional, Soleilhac, Jean Marc, additional, Lanté, Fabien, additional, Kumar, Atul, additional, Pero, Maria Elena, additional, Martínez-Hernández, José, additional, Corrao, Charlotte, additional, Falivelli, Giulia, additional, Payet, Floriane, additional, Gory-Fauré, Sylvie, additional, Bosc, Christophe, additional, Blanca Ramirez, Marian, additional, Sproul, Andrew, additional, Brocard, Jacques, additional, Di Cara, Benjamin, additional, Delagrange, Philippe, additional, Buisson, Alain, additional, Goldberg, Yves, additional, Moutin, Marie Jo, additional, Bartolini, Francesca, additional, and Andrieux, Annie, additional

Published
2022
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18. 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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21. 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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22. Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy

Author

Tadmouri, Abir, Kiyonaka, Shigeki, Barbado, Maud, Rousset, Matthieu, Fablet, Katell, Sawamura, Seishiro, Bahembera, Eloi, Pernet‐Gallay, Karin, Arnoult, Christophe, Miki, Takafumi, Sadoul, Karin, Gory‐Faure, Sylvie, Lambrecht, Caroline, Lesage, Florian, Akiyama, Satoshi, Khochbin, Saadi, Baulande, Sylvain, Janssens, Veerle, Andrieux, Annie, Dolmetsch, Ricardo, Ronjat, Michel, Mori, Yasuo, and De Waard, Michel

Published
2012
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26. 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

27. Tubulin post‐translational modifications control neuronal development and functions

Author

Moutin, Marie‐Jo, Bosc, Christophe, Peris, Leticia, Andrieux, Annie, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Moutin, Marie-Jo

Subjects
neuro‐diseases, neuro-diseases, Acetylation, Review Article, macromolecular substances, tyrosination, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Microtubules, neuron, tubulin, post-translational modifications, post‐translational modifications, Review Articles, Protein Processing, Post-Translational, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cytoskeleton
Abstract

International audience; Microtubules (MTs) are an essential component of the neuronal cytoskeleton; they are involved in various aspects of neuron development, maintenance, and functions including polarization, synaptic plasticity, and transport. Neuronal MTs are highly heterogeneous due to the presence of multiple tubulin isotypes and extensive post-translational modifications (PTMs). These PTMs—most notably detyrosination, acetylation, and polyglutamylation—have emerged as important regulators of the neuronal microtubule cytoskeleton. With this review, we summarize what is currently known about the impact of tubulin PTMs on microtubule dynamics, neuronal differentiation, plasticity, and transport as well as on brain function in normal and pathological conditions, in particular during neuro-degeneration. The main therapeutic approaches to neuro-diseases based on the modulation of tubulin PTMs are also summarized. Overall, the review indicates how tubulin PTMs can generate a large number of functionally specialized microtubule sub-networks, each of which is crucial to specific neuronal features.

Published
2020
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28. A high variability of arterial Doppler waveform descriptions exists in China

Author

Bouet, Valentine, Percelay, Solenn, Leroux, Elise, Diarra, Boubacar, Leger, Marianne, Delcroix, Nicolas, Andrieux, Annie, Dollfus, Sonia, Freret, Thomas, Boulouard, Michel, Peking University [Beijing], Austin Hospital [Melbourne], Austin Health, Jobst Vascular Institute [Promedica Toledo Hospital], Mobilités : Vieillissement, Pathologie, Santé (COMETE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], 7172209, Natural Science Foundation of Beijing Municipality, Université de Caen Normandie - UFR Santé (UNICAEN Santé), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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 (UGA), Service de psychiatrie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
China, medicine.medical_specialty, Doppler classification, duplex ultrasound, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, peripheral artery disease, 030218 nuclear medicine & medical imaging, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Doppler waveform, Humans, Medicine, Peripheral artery disease (PAD), ComputingMilieux_MISCELLANEOUS, vascular imaging/diagnostics, Observer Variation, business.industry, Reproducibility of Results, Ultrasonography, Doppler, Arteries, medicine.disease, [SDV] Life Sciences [q-bio], Cardiology, Doppler waveforms, Cardiology and Cardiovascular Medicine, business
Abstract

International audience

Published
2020
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30. 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

31. 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

36. The suppression of brain cold-stable microtubules in mice induces synaptic defects associated with neuroleptic-sensitive behavioral disorders

Author

Andrieux, Annie, Salin, Paul A., Vernet, Muriel, Kujala, Pekka, Baratier, Julie, Gory-Faure, Sylvie, Bosc, Christophe, Pointu, Herve, Proietto, Dominique, Schweitzer, Annie, Denarier, Eric, Klumperman, Jucith, and Job, Dider

Subjects
Cytochemistry -- Research, Synapses -- Genetic aspects, Mice, mutant strains -- Usage, Microtubules -- Physiological aspects, Biological sciences
Abstract

Suppression of brain cold-stable microtubules in mice has been found to induce synaptic defects associated with neuroleptic-sensitive behavioral disorders. STOP-null mice, lacking cold-stable microtubules, were generated, and surprisingly, they had no detectable defects in brain anatomy, but had synaptic defects. Stop-null mice may lead to a model for study of neuroleptics in illnesses such as schizophrenia, which is thought to come from synaptic defects.

Published
2002

38. 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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39. A New Quantitative Cell-Based Assay Reveals Unexpected Microtubule Stabilizing Activity of Certain Kinase Inhibitors, Clinically Approved or in the Process of Approval

Author

Ramirez-Rios, Sacnicte, primary, Michallet, Sophie, additional, Peris, Leticia, additional, Barette, Caroline, additional, Rabat, Clotilde, additional, Feng, Yangbo, additional, Fauvarque, Marie-Odile, additional, Andrieux, Annie, additional, Sadoul, Karin, additional, and Lafanechère, Laurence, additional

Published
2020
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40. 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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41. 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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42. 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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43. Schizophrenia: validity of a 3-hit mouse model

Author

Percelay, Solenn, Freret, Thomas, Diarra, Boubacar, Delcroix, Nicolas, Leroux, Elise, Andrieux, Annie, Dollfus, Sonia, Boulouard, Michel, BouËt, Valentine, Mobilités : Vieillissement, Pathologie, Santé (COMETE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Reference Health Center of the district of Ouelessebougou [Ouelessebougou, Mali], Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques de la Schizophrénie (ISTS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Federation of European Neuroscience Societies, Percelay, Solenn, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), and 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)

Subjects
[SCCO]Cognitive science, model, mice, parvalbumin-positive neurons, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Schizophrenia, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, imaging, [SCCO] Cognitive science, behaviour
Abstract

International audience; Schizophrenia is a frequent psychiatric disease (prevalence 1%). Unfortunately, current treatments are unsatisfactory: they do not cover the entirety of symptoms, they can even worsen them, and they are inefficient in 30% of patients. There is a crucial need for new drugs, which requires more relevant animal models taking into account the multifactorial nature of this pathology. We built a new animal model gathering three factors: a genetic predisposition (partial deletion of the MAP6 (Microtubule-Associated Protein 6) with an early post-natal stress (maternal separation at the age of 9 days during 24h) and a late disturbance during adolescence (THC from post-natal day 32 to 52; 8 mg/kg). A particular focus was made on behavior, brain imaging, and immunohistochemistry. The 3-hit combination induces specific decrease in spontaneous activity in the open-field, in sociability in the approach-avoidance test, and in working memory performances. In vivo and post-mortem MRI revealed a decrease in cortical thickness and in hippocampus volume, and a loss of integrity of callosal fibers (less axons, less myelin). Moreover, a decrease in density of parvalbumin-positive neurons was observed in CA1 of hippocampus. To conclude, 3-hit combination causes several symptoms mimicking negative and cognitive symptoms of schizophrenia, accompanied with structural changes bringing a high face validity. Moreover, it possesses a strong construct validity which fits with gene x environment interactions hypothesis of schizophrenia. The predictive validity is currently investigated by using lurasidone. The model is expected to be a powerful tool to test new therapeutic strategies for the treatment of schizophrenia.

Published
2018

44. Additional file 7: of Deletion of the microtubule-associated protein 6 (MAP6) results in skeletal muscle dysfunction

Author

Sébastien, Muriel, Benoit Giannesini, Aubin, Perrine, Brocard, Julie, Chivet, Mathilde, Pietrangelo, Laura, Boncompagni, Simona, Bosc, Christophe, Brocard, Jacques, Rendu, John, Gory-Fauré, Sylvie, Andrieux, Annie, Fourest-Lieuvin, Anne, Fauré, Julien, and Marty, Isabelle

Abstract

Table S2. Quantification of triads analyzed by EM. (DOCX 15 kb)

Published
2018
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45. Additional file 3: of Deletion of the microtubule-associated protein 6 (MAP6) results in skeletal muscle dysfunction

Author

Sébastien, Muriel, Benoit Giannesini, Aubin, Perrine, Brocard, Julie, Chivet, Mathilde, Pietrangelo, Laura, Boncompagni, Simona, Bosc, Christophe, Brocard, Jacques, Rendu, John, Gory-Fauré, Sylvie, Andrieux, Annie, Fourest-Lieuvin, Anne, Fauré, Julien, and Marty, Isabelle

Abstract

Table S1. Gastrocnemius muscle bioenergetics assessed in vivo using 31P-MRS. (DOCX 15 kb)

Published
2018
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46. Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility

Author

Giordano, Tiziana, primary, Gadadhar, Sudarshan, additional, Bodakuntla, Satish, additional, Straub, Jonas, additional, Leboucher, Sophie, additional, Martinez, Guillaume, additional, Chemlali, Walid, additional, Bosc, Christophe, additional, Andrieux, Annie, additional, Bieche, Ivan, additional, Arnoult, Christophe, additional, Geimer, Stefan, additional, and Janke, Carsten, additional

Published
2019
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47. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

Author

Aunis Dominique, Van Dorsselaer Alain, Bianchi Enrica, Delalande François, Stuber Denise, Deloulme Jean-Christophe, Schweitzer Annie, Kemmel Véronique, Laux Alexis, Muller Arnaud H, Charlet Alexandre, Andrieux Annie, Poisbeau Pierrick, and Goumon Yannick

Subjects
Pathology, RB1-214
Abstract

Abstract Background- Mice deficient for the stable tubule only peptide (STOP) display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p.) produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg) was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg) was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

Published
2010
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48. 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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49. 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

50. CAP-Gly proteins contribute to microtubule-dependent trafficking via interactions with the C-terminal aromatic residue of α-tubulin

Author

Andrieux, Annie, Aubry, Laurence, Boscheron, Cécile, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), 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), 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), [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]), and Bertacchi Griffi, Nathalie

Subjects
p150Glued, [SDV]Life Sciences [q-bio], fungi, Brief Report - Commissioned, Biological Transport, [SDV] Life Sciences [q-bio], microtubules, trafficking, Tubulin, +Tips tyrosination, Animals, Humans, CLIP170, endosome, Microtubule-Associated Proteins, ComputingMilieux_MISCELLANEOUS
Abstract

SUMMARY In mammals, the C-terminal tyrosine residue of α-tubulin is subjected to removal/re-addition cycles resulting in tyrosinated microtubules and detyrosinated Glu-microtubules. CLIP170 and its yeast ortholog (Bik1) interact weakly with Glu-microtubules. Recently, we described a Microtubule- Rho1- and Bik1-dependent mechanism involved in Snc1 routing. Here, we further show a contribution of the yeast p150Glued ortholog (Nip100) in Snc1 trafficking. Both CLIP170 and p150Glued are CAP-Gly-containing proteins that belong to the microtubule +end-tracking protein family (known as +Tips). We discuss the +Tips-dependent role of microtubules in trafficking, the role of CAP-Gly proteins as possible molecular links between microtubules and vesicles, as well as the contribution of the Rho1-GTPase to the regulation of the +Tips repertoire and the partners associated with microtubules.

Published
2017
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