Actin scaffolding by clathrin heavy chain is required for skeletal muscle sarcomere organization

Stéphane Vassilopoulos; Christel Gentil; Jeanne Lainé; Pierre-Olivier Buclez; Agathe Franck; Arnaud Ferry; Guillaume Précigout; Robyn Roth; John E Heuser; Frances M Brodsky; Luis Garcia; Gisèle Bonne; Thomas Voit; France Piétri-Rouxel; Marc Bitoun

doi:10.1083/jcb.201309096

Actin scaffolding by clathrin heavy chain is required for skeletal muscle sarcomere organization

J Cell Biol. 2014 May 12;205(3):377-93. doi: 10.1083/jcb.201309096. Epub 2014 May 5.

Authors

Stéphane Vassilopoulos¹, Christel Gentil, Jeanne Lainé, Pierre-Olivier Buclez, Agathe Franck, Arnaud Ferry, Guillaume Précigout, Robyn Roth, John E Heuser, Frances M Brodsky, Luis Garcia, Gisèle Bonne, Thomas Voit, France Piétri-Rouxel, Marc Bitoun

Affiliation

¹ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Actin Cytoskeleton / metabolism*
Actinin / metabolism
Actins / metabolism*
Adaptor Proteins, Signal Transducing
Animals
Clathrin Heavy Chains / genetics
Clathrin Heavy Chains / metabolism*
Costameres / metabolism*
Costameres / pathology
DNA-Binding Proteins / metabolism
Dependovirus / genetics
Dynamin II / metabolism
Gene Transfer Techniques
Genetic Vectors
Mice
Mice, Inbred C57BL
Microfilament Proteins
Muscle Contraction
Muscle Fibers, Skeletal / metabolism*
Muscle Fibers, Skeletal / pathology
Muscle Strength
Muscular Dystrophies / metabolism
Muscular Dystrophies / pathology
Muscular Dystrophies / physiopathology
Myopathies, Structural, Congenital / metabolism
Myopathies, Structural, Congenital / pathology
Myopathies, Structural, Congenital / physiopathology
Sarcomeres / metabolism*
Sarcomeres / pathology
Time Factors

Substances

Actins
Adaptor Proteins, Signal Transducing
DNA-Binding Proteins
Hip1r protein, mouse
Microfilament Proteins
Actinin
Clathrin Heavy Chains
Dynamin II

Abstract

Publication types

MeSH terms

Substances

Grants and funding