title: Actin scaffolding by clathrin heavy chain is required for skeletal muscle sarcomere organization.
abstract: The ubiquitous clathrin heavy chain (CHC), the main component of clathrin-coated vesicles, is well characterized for its role in intracellular membrane traffic and endocytosis from the plasma membrane (PM). Here, we demonstrate that in skeletal muscle CHC regulates the formation and maintenance of PM-sarcomere attachment sites also known as costameres. We show that clathrin forms large coated lattices associated with actin filaments and the muscle-specific isoform of α-actinin at the PM of differentiated myotubes. Depletion of CHC in myotubes induced a loss of actin and α-actinin sarcomeric organization, whereas CHC depletion in vivo induced a loss of contractile force due to the detachment of sarcomeres from the PM. Our results suggest that CHC contributes to the formation and maintenance of the contractile apparatus through interactions with costameric proteins and highlight an unconventional role for CHC in skeletal muscle that may be relevant to pathophysiology of neuromuscular disorders.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U974, 2 Centre National de la Recherche Scientifique (CNRS) UMR 7215, and 3 Université Pierre et Marie Curie-Paris 6, UM 76, Paris F-75013, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vassilopoulos
authors.forename: Christel
authors.initials: C
authors.lastname: Gentil
authors.forename: Jeanne
authors.initials: J
authors.lastname: Lainé
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Buclez
authors.forename: Agathe
authors.initials: A
authors.lastname: Franck
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.forename: Guillaume
authors.initials: G
authors.lastname: Précigout
authors.forename: Robyn
authors.initials: R
authors.lastname: Roth
authors.forename: John E
authors.initials: JE
authors.lastname: Heuser
authors.forename: Frances M
authors.initials: FM
authors.lastname: Brodsky
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia
authors.forename: Gisèle
authors.initials: G
authors.lastname: Bonne
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: France
authors.initials: F
authors.lastname: Piétri-Rouxel
authors.forename: Marc
authors.initials: M
authors.lastname: Bitoun
mesh_terms: D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000378:metabolism*; D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D033922:Clathrin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D054974:Costameres / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D034285:Dynamin II / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D053580:Muscle Strength; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020914:Myopathies, Structural, Congenital / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012518:Sarcomeres / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489534:Hip1r protein, mouse; D008840:Microfilament Proteins; D000185:Actinin; D033922:Clathrin Heavy Chains; D034285:Dynamin II