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N‐WASP is required for Amphiphysin‐2/BIN1‐dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathy

2014Journal article Open access
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dc.contributor.authorFalcone, Sestina
dc.contributor.authorRoman, William
dc.contributor.authorHnia, Karim
dc.contributor.authorGache, Vincent
dc.contributor.authorDidier, Nathalie
dc.contributor.authorLainé, Jeanne
dc.contributor.authorAuradé, Frederic
dc.contributor.authorMarty, Isabelle
dc.contributor.authorNishino, Ichizo
dc.contributor.authorCharlet‐Berguerand, Nicolas
dc.contributor.authorRomero, Norma Beatriz
dc.contributor.authorMarazzi, Giovanna
dc.contributor.authorSassoon, David
dc.contributor.authorLaporte, Jocelyn
dc.contributor.authorGomes, Edgar
dc.date.accessioned2022-02-15T15:14:40Z
dc.date.available2022-02-15T15:14:40Z
dc.date.issued2014
dc.description© 2014 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.pt_PT
dc.description.abstractMutations in amphiphysin-2/BIN1, dynamin 2, and myotubularin are associated with centronuclear myopathy (CNM), a muscle disorder characterized by myofibers with atypical central nuclear positioning and abnormal triads. Mis-splicing of amphiphysin-2/BIN1 is also associated with myotonic dystrophy that shares histopathological hallmarks with CNM. How amphiphysin-2 orchestrates nuclear positioning and triad organization and how CNM-associated mutations lead to muscle dysfunction remains elusive. We find that N-WASP interacts with amphiphysin-2 in myofibers and that this interaction and N-WASP distribution are disrupted by amphiphysin-2 CNM mutations. We establish that N-WASP functions downstream of amphiphysin-2 to drive peripheral nuclear positioning and triad organization during myofiber formation. Peripheral nuclear positioning requires microtubule/Map7/Kif5b-dependent distribution of nuclei along the myofiber and is driven by actin and nesprins. In adult myofibers, N-WASP and amphiphysin-2 are only involved in the maintenance of triad organization but not in the maintenance of peripheral nuclear positioning. Importantly, we confirmed that N-WASP distribution is disrupted in CNM and myotonic dystrophy patients. Our results support a role for N-WASP in amphiphysin-2-dependent nuclear positioning and triad organization and in CNM and myotonic dystrophy pathophysiology.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEMBO Mol Med (2014)6:1455–1475pt_PT
dc.identifier.doi10.15252/emmm.201404436pt_PT
dc.identifier.eissn1757-4684
dc.identifier.issn1757-4676
dc.identifier.urihttp://hdl.handle.net/10451/51321
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherEMBO Presspt_PT
dc.relation.publisherversionhttps://www.embopress.org/journal/17574684pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCentronuclear myopathypt_PT
dc.subjectCytoskeletonpt_PT
dc.subjectNuclear movementpt_PT
dc.subjectTriad formationpt_PT
dc.titleN‐WASP is required for Amphiphysin‐2/BIN1‐dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1475pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1455pt_PT
oaire.citation.titleEMBO Molecular Medicinept_PT
oaire.citation.volume6pt_PT
person.familyNameGomes
person.givenNameEdgar
person.identifier.ciencia-id6215-9445-3042
person.identifier.orcid0000-0002-6941-4872
person.identifier.ridD-9000-2015
person.identifier.scopus-author-id7102464212
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationbd5022e4-63ff-4d9e-b4f4-3fc163836720
relation.isAuthorOfPublication.latestForDiscoverybd5022e4-63ff-4d9e-b4f4-3fc163836720

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