Résumé :
|
Clathrin CHC17, the ubiquitous clathrin heavy chain encoded on human chromosome 17, is the main component of clathrin coated vesicles (CCV), well characterized for its role in vesicle formation during endocytosis of membrane receptors from the plasma membrane and from intracellular compartments such as the trans-golgi network (TGN) and endosomes. The possible role of clathrin heavy chain in organizing the contractile apparatus and its early striated expression pattern during muscle differentiation was put forth a few years ago (Kaufman et al., 1990) but these observations were never pursued in order to establish the function of clathrin during myogenesis. Here we used an exon skipping strategy through optimized U7snRNA and AAV-mediated gene transfer to achieve long-lasting in-vivo knockdown of CHC17 in mouse muscle and tested the contribution of clathrin in maintenance of muscle ultrastructure. CHC17 depletion induced sarcomeric disorganisation with streaming of the Z-line 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 integrins, vinculin and other costameric proteins and highlight an unconventional role for CHC17 in skeletal muscle which may be relevant to muscle physiology and could be associated to muscle diseases of unknown aetiology.
|