Résumé :
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Desminopathies are subgroups of myofibrillar myopathies caused by mutations in desmin gene. They are characterized by the presence of protein aggregates in muscle cells. Desmin is the main IF protein in mature striated muscle and it is found at the sarcolemma, Z-lines, neuromuscular and myotendinous junctions. Several other IF or IFAP proteins are characterized in muscle: vimentin, nestin, syncoilin, and synemin, all containing the typical coiled-coil domains of IF proteins. The screening of many groups of DRM patients shows that synemin associated with muscle protein aggregates. Synemin gene is located on human chromosome 15. It encoded three isoforms (180, 150 and 41 kDa) produced by alternative splicing according to the tissue types: muscles, lens, astrocytes and neurons (Xue et al. 2004). During mouse development, the synemin isoforms show a dynamic and complex distribution. The synemin M was present as early as E5 with vimentin and nestin. Synemin H was found later in nervous and mesoderm derivatives, in E9 embryo when vasculogenesis, somitogenesis and the migration of neural crest cells are under way in the embryo. Later, synemin L was detected in neurons from E13 and in muscle of adult (Izmiryan et al, 2006). None of the three synemin isoforms becomes organized into filaments without an appropriate copolymerization partner. Using a series of constructs by site-directed mutagenesis with substitutions in the 2A and 2B subdomains of synemin and a series of chimeric synemins having the vimentin head, we have showed that the formation of the filamentous homopolymers required at least a vimentin-like head domain and the 2A and 2B regions of the rod domain. The co-localization of synemins with desmin in normal and myopathic muscles, with vimentin in endothelial cells and of synemin with neurofilaments or peripherin in neurons indicates that synemins are key cross-linking proteins connected with different cytoskeletal structures.
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