Titre :
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A role for clathrin heavy chain in costamere formation and maintenance
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Auteurs :
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Xèmes Journées Annuelles de la Société française de Myologie (SFM) (14-16 novembre 2012; Grenoble (France)) ;
Gentil C ;
Laine J ;
Buclez PO ;
Ferry A ;
Brodsky FM ;
Bonne G ;
Voit T ;
Garcia L ;
Pietri Rouxel F ;
Bitoun M
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Type de document :
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Article
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Editeur :
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Société Française de Myologie SFM, 2012
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Pages :
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p. 35
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Langues:
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Anglais
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Mots-clés :
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ARN interférent
;
clathrine
;
costamère
;
dégenérescence de la fibre musculaire
;
endocytose
;
interaction protéine-protéine
;
muscle squelettique
;
myopathie centronucléaire autosomique dominante liée à dynamine 2
;
régénération musculaire
;
sarcomère
;
transport intracellulaire
;
vecteur adénoassocié
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Résumé :
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Several diseases are caused by mutations in genes encoding proteins belonging to the intracellular membrane trafficking machinery. Recent work from our team, interested in centronuclear myopathy caused by mutations in dynamin 2 has suggested that a clathrin-dependent endocytosis defect might be a central pathophysiologic mechanism of this pathology. Clathrin heavy chain (CHC) is the main component of clathrin coated vesicles, well characterized for its role in vesicle formation during endocytosis and trafficking from intracellular compartments. The possible role of CHC in organizing the contractile apparatus was put forth a few years ago but these observations were never pursued in order to establish the function of clathrin during myogenesis. Here we used an siRNA-mediated CHC knock-down in-vitro strategy and an shRNA combined to AAV-mediated gene transfer to achieve in-vivo knockdown. CHC depletion induced sarcomeric disorganisation and led to rapid muscle degeneration and subsequent regeneration. Our results raise the possibility that clathrin heavy chain contributes to sarcomeric structure through interactions with costameric proteins and highlight a role for CHC in skeletal muscle which may be relevant to muscle physiology and could be associated to muscle diseases of unknown aetiology.
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