The cell polarity protein Vangl2 in the muscle shapes the neuromuscular synapse by binding to and regulating the tyrosine kinase MuSK
| Autor: | Myriam Boëx, Steve Cottin, Marius Halliez, Stéphanie Bauché, Céline Buon, Nathalie Sans, Mireille Montcouquiol, Jordi Molgó, Muriel Amar, Arnaud Ferry, Mégane Lemaitre, Andrée Rouche, Dominique Langui, Asha Baskaran, Bertrand Fontaine, Julien Messéant, Laure Strochlic |
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| Přispěvatelé: | Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT), 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), Phénotypage du petit animal (UMS28), Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Strochlic, Laure |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Muscle Fibers Skeletal Cell Polarity Nerve Tissue Proteins Cell Biology [SDV.BC]Life Sciences [q-bio]/Cellular Biology Protein-Tyrosine Kinases Biochemistry [SDV] Life Sciences [q-bio] Fatty Acids Monounsaturated Mice Synapses Animals Receptors Cholinergic Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology |
| Zdroj: | Science Signaling Science Signaling, 2022, 15 (734), pp.eabg4982. ⟨10.1126/scisignal.abg4982⟩ |
| ISSN: | 1937-9145 |
| Popis: | The development of the neuromuscular junction (NMJ) requires dynamic trans-synaptic coordination orchestrated by secreted factors, including Wnt family morphogens. To investigate how these synaptic cues in NMJ development are transduced, particularly in the regulation of acetylcholine receptor (AChR) accumulation in the postsynaptic membrane, we explored the function of Van Gogh–like protein 2 (Vangl2), a core component of Wnt planar cell polarity signaling. We found that conditional, muscle-specific ablation of Vangl2 in mice reproduced the NMJ differentiation defects seen in mice with global Vangl2 deletion. These alterations persisted into adulthood and led to NMJ disassembly, impaired neurotransmission, and deficits in motor function. Vangl2 and the muscle-specific receptor tyrosine kinase MuSK were functionally associated in Wnt signaling in the muscle. Vangl2 bound to and promoted the signaling activity of MuSK in response to Wnt11. The loss of Vangl2 impaired RhoA activation in cultured mouse myotubes and caused dispersed, rather than clustered, organization of AChRs at the postsynaptic or muscle cell side of NMJs in vivo. Our results identify Vangl2 as a key player of the core complex of molecules shaping neuromuscular synapses and thus shed light on the molecular mechanisms underlying NMJ assembly. |
| Databáze: | OpenAIRE |
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