Résumé :
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Communication n° 22. Dystroglycan is part of an adhesion receptor complex linking the extracellular matrix to the actin cytoskeleton. Previous studies have implicated dystroglycan in basement membrane formation and as a crucial link between dystrophin and laminin in muscle. We report here a further novel function for dystroglycan which appears to be in addition to its role as an adhesion molecule. b-dystroglycan has been localised to microvilli structures in a number of cell types where it associates with the cytoskeletal adaptor ezrin, through which it is able to modulate the actin cytoskeleton and induce peripheral filopodia and microvilli. Ezrin is able to interact with dystroglycan through a cluster of basic residues in the juxtamembrane region of dystroglycan, and mutation of these residues both prevents ezrin binding and the induction of actin-rich surface protrusions. Analysis of the mechanism by which dystroglycan induces filopodia has revealed an association between dystroglycan and the GTP exchange factor Dbl. Furthermore, dystroglycan is able to recruit both Dbl and Cdc42 to peripheral sites in cells. Expression of a cytoplasmic fragment of dystroglycan results in the localisation of Cdc42 to intracellular sites and the suppression of filopodia formation. These data suggest that in addition to a role for dystroglycan as a scaffold for the ERK MAP kinase cascade, and as a substrate for adhesion-mediated tyrosine phosphorylation, dystroglycan can also regulate the actin cytoskeleton by modulating the Rho family GTPase signalling machinery. These studies reveal novel functions and additional signalling roles for dystroglycan, raising the possibility of new avenues for therapeutic intervention in diseases such as Duchenne muscular dystrophy.
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