Deletion of the microtubule-associated protein 6 (MAP6) results in skeletal muscle dysfunction

Autor:	Sylvie Gory-Fauré, Annie Andrieux, Mathilde Chivet, Christophe Bosc, Laura Pietrangelo, Julie Brocard, Muriel Sébastien, Isabelle Marty, Perrine Aubin, Benoît Giannesini, Anne Fourest-Lieuvin, John Rendu, Jacques Brocard, Simona Boncompagni, Julien Fauré
Přispěvatelé:	INSERM U836, équipe 4, Muscles et pathologies, 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), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), University 'G. d'Annunzio' of Chieti-Pescara [Chieti], INSERM U836, équipe 1, Physiopathologie du cytosquelette, Organisation Fonctionnelle du Cytosquelette, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR27, Université de Montpellier (UM), Canaux calciques , fonctions et pathologies, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Association Française contre lesMyopathies (AFM-Téléthon) to MS, PA, and IM, and from Italian Ministry ofHealth - GR2011-02352681 to SB, Giannesini, Benoit, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), [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])
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	Male 0301 basic medicine lcsh:Diseases of the musculoskeletal system [SDV]Life Sciences [q-bio] Muscle Fibers Skeletal Triad Sarcoplasmic reticulum [SDV.BC]Life Sciences [q-bio]/Cellular Biology Microtubules Mice 03 medical and health sciences Microtubule medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Orthopedics and Sports Medicine [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Calcium Signaling MAP6 Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology Cells Cultured Calcium release Chemistry Myogenesis Microtubule-associated protein Muscle weakness Skeletal muscle Cell Biology Muscle atrophy Cell biology Mice Inbred C57BL [SDV] Life Sciences [q-bio] 030104 developmental biology medicine.anatomical_structure Muscle contraction Knockout mouse Female medicine.symptom lcsh:RC925-935 Microtubule-Associated Proteins Gene Deletion
Zdroj:	Skeletal Muscle, Vol 8, Iss 1, Pp 1-14 (2018) Skeletal Muscle Skeletal Muscle, 2018, 8 (1), ⟨10.1186/s13395-018-0176-8⟩ Skeletal Muscle, BioMed Central, 2018, 8 (1), ⟨10.1186/s13395-018-0176-8⟩
ISSN:	2044-5040
Popis:	Background The skeletal muscle fiber has a specific and precise intracellular organization which is at the basis of an efficient muscle contraction. Microtubules are long known to play a major role in the function and organization of many cells, but in skeletal muscle, the contribution of the microtubule cytoskeleton to the efficiency of contraction has only recently been studied. The microtubule network is dynamic and is regulated by many microtubule-associated proteins (MAPs). In the present study, the role of the MAP6 protein in skeletal muscle organization and function has been studied using the MAP6 knockout mouse line. Methods The presence of MAP6 transcripts and proteins was shown in mouse muscle homogenates and primary culture using RT-PCR and western blot. The in vivo evaluation of muscle force of MAP6 knockout (KO) mice was performed on anesthetized animals using electrostimulation coupled to mechanical measurement and multimodal magnetic resonance. The impact of MAP6 deletion on microtubule organization and intracellular structures was studied using immunofluorescent labeling and electron microscopy, and on calcium release for muscle contraction using Fluo-4 calcium imaging on cultured myotubes. Statistical analysis was performed using Student’s t test or the Mann-Whitney test. Results We demonstrate the presence of MAP6 transcripts and proteins in skeletal muscle. Deletion of MAP6 results in a large number of muscle modifications: muscle weakness associated with slight muscle atrophy, alterations of microtubule network and sarcoplasmic reticulum organization, and reduction in calcium release. Conclusion Altogether, our results demonstrate that MAP6 is involved in skeletal muscle function. Its deletion results in alterations in skeletal muscle contraction which contribute to the global deleterious phenotype of the MAP6 KO mice. As MAP6 KO mouse line is a model for schizophrenia, our work points to a possible muscle weakness associated to some forms of schizophrenia.
Databáze:	OpenAIRE
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