Titre : | Calcium dependent proteolysis and muscle cell motility (abstract : congrès international de Myologie, 2005) |
contenu dans : | |
Auteurs : | Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ; Mazères G ; Leloup L ; Cottin P ; Brustis JJ |
Type de document : | Article |
Année de publication : | 2005 |
Pages : | p. 80 |
Langues: | Anglais |
Mots-clés : | calcium ; calpaïne ; calpastatine ; colloque ; cycle cellulaire ; différenciation musculaire ; fusion cellulaire ; migration cellulaire ; mobilité cellulaire ; muscle squelettique ; myoblaste ; myogenèse ; protéine cytosquelettique ; protéine MARCKS ; protéolyse musculaire |
Résumé : |
Communication n° 443. Introduction : The calcium dependent proteolytic system, composed of ubiquitous and tissue specific calpains, is involved in many physiological events such as cell cycle, muscle cell differentiation, cell spreading and motility. The deregulation of calpain activity leads to calpainopathies including cataract, neurodegenerative diseases and muscular dystrophies. Concerning more specifically muscle cell differentiation, µ- and m-calpains are known to play pivotal roles during the earlier myogenesis steps, in particular during myoblasts fusion. Objectives : The objectives of our research are to elucidate the role of ubiquitous calpains in myoblast motility, a crucial step of muscle formation. Methods : For this study we have carried out experiments such as: - Calpain inhibitors treatments. - Clonal C2C12 line over-expressing calpastatin (endogenous inhibitor of calpains). - Antisens treatments against µ- and m-calpains. - Transfections to increase or decrease MARCKS protein (Myristoylated Alanin Rich C Kinase Substrate). Results : Calpain inhibitors treatments, as well as calpastatin over-expression, as antisense strategies against calpains decrease dramatically the rates of myoblast migration, adhesion and spreading. Inhibition of calpains induces also an accumulation of MARCKS, a calpain substrate localized at focal adhesion; the diminution of MARCKS expression increases significantly the C2C12 motility. On the other side, an over-expression of MARCKS induces a decrease of myoblast motility. Conclusion : All these results show that calpains are involved in myoblast migration, stress fiber organization, membrane protusions formation and cell adhesion. According to antisense strategy, the roles of µ- and m-calpains seem to be different. Furthermore myoblast migration is dependent on MARCKS presence and MARCKS cellular localization. Our results show also that myoblast motility is dependent on MARCKS phosphorylation through PKC-a activation. The role of calpains in cytoskeletal organization and the identification of other calpain substrates involved in myoblast motility are under investigations. |