Actin scaffolding by clathrin heavy chain and dynamin2 in skeletal muscle

Orateur : Stéphane VASSILOPOULOS (Institut de Myologie, UPMC-INSERM, Paris)

Costameres are muscle-specific sub-sarcolemmal protein assemblies originally described as electron-dense plaques rich in focal adhesion markers (Danowski et al., 1992 ; Pardo et al., 1983 ; Shear and Bloch, 1985) which represent specialized focal adhesion sites of muscle fibers, located between the plasma membrane (PM) and sarcomeres, the contractile units of muscle. Costameres play both a mechanical and a signaling role during contraction, transmitting force from the contractile apparatus to the extracellular matrix in order to stabilize muscle fibers. In addition to their role in cell attachment, they are an important site for the initial events in new sarcomere formation and established components of the mechanosensory apparatus. Any defect in the structure of the costamere resulting in its disorganization induces a muscle weakness and a myopathy. Our results demonstrate the existence of a newly identified costamere complex centered on large, honeycomb shaped, clathrin plaques (flat lattices) at the PM of myotubes (Vassilopoulos et al., 2014). These plaques, not classically associated with the role of clathrin in endocytosis, constitute a pre-requisite for sarcomere formation. Along this line, our hypothesis is that the muscle weakness observed in centronuclear myopathy patients with mutations in Dynamin 2 results at least in part from an alteration of sarcomere contractile properties, which originates from an alteration in clathrin plaque function and subsequently strongly perturbs the functional link between sarcomeres and the PM. Vassilopoulos S, Gentil C, Lainé J, Buclez PO, Franck A, Ferry A, Précigout G, Roth R, Heuser JE, Brodsky FM, Garcia L, Bonne G, Voit T, Piétri-Rouxel F, Bitoun M. Actin scaffolding by clathrin heavy chain is required for skeletal muscle sarcomere organization. J Cell Biol. (2014) 205, 377-93.

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