Author:
Hakibilen Coralie,Delort Florence,Daher Marie-Thérèse,Joanne Pierre,Cabet Eva,Cardoso Olivier,Bourgois-Rocha Fany,Tian Cuixia,Rivas Eloy,Madruga Marcos,Ferreiro Ana,Lilienbaum Alain,Vicart Patrick,Agbulut Onnik,Hénon Sylvie,Batonnet-Pichon Sabrina
Abstract
Cellular adhesion and migration are key functions that are disrupted in numerous diseases. We report that desmin, a type-III muscle-specific intermediate filament, is a novel cell adhesion regulator. Expression of p.R406W mutant desmin, identified in patients with desmin-related myopathy, modified focal adhesion area and expression of adhesion-signaling genes in myogenic C2C12 cells. Satellite cells extracted from desmin-knock-out (DesKO) and desmin-knock-in-p.R405W (DesKI-R405W) mice were less adhesive and migrated faster than those from wild-type mice. Moreover, we observed mislocalized and aggregated vinculin, a key component of cell adhesion, in DesKO and DesKI-R405W muscles. Vinculin expression was also increased in desmin-related myopathy patient muscles. Together, our results establish a novel role for desmin in cell-matrix adhesion, an essential process for strength transmission, satellite cell migration and muscle regeneration. Our study links the patho-physiological mechanisms of desminopathies to adhesion/migration defects, and may lead to new cellular targets for novel therapeutic approaches.
Funder
Université Paris Diderot
Association Française Contre les Myopathies
Agence Nationale de la Recherche
Centre National de la Recherche Scientifique
Subject
Cell Biology,Developmental Biology
Cited by
7 articles.
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