Skeletal muscle cells are composed of contractile elements wrapped in a membrane network. Formation and maintenance of skeletal muscle involve muscle precursor migration, fusion and triad formation. These events rely on actin cytoskeleton and membrane remodelling in muscle cells. The aim of my thesis work was to study the role of the scaffold protein CKIP-1 (casein kinase 2 interacting protein-1) at different steps of skeletal muscle development. We identified the actin nucleation complex Arp (actin-related protein) 2/3 as a CKIP-1 new interactor and showed that Ckip-1 depletion in zebrafish embryos alters fast twitch myoblast morphology and prevents their fusion due to actin cytoskeleton disorganization. I further showed that CKIP-1 is only present during early myogenesis in vitro and in vivo in mouse, and is then cleaved. Modulation of CKIP-1 expression induces membrane defects in vitro but also in vivo in adult mouse muscle, suggesting that CKIP-1 is involved in membrane remodelling. Through its abilities to remodel actin cytoskeleton and thus membranes, CKIP-1 could be implicated in various steps of muscle life: myoblast migration, fusion, and formation or maintenance of the intracellular membrane compartments of skeletal muscle cells.
