Rac1 and RhoA GTPases have antagonistic functions during N-cadherin-dependent cell-cell contact formation in C2C12 myoblasts.

Franck Comunale (1) , Marie Causeret (1) , Cyril Favard , Julien Cau (1) , Nicolas Taulet (1) , Sophie Charrasse (1) , Cécile Gauthier-Rouvière (1)

1 CRBM - Centre de recherche en Biologie Cellulaire

BACKGROUND INFORMATION: N-cadherin, a member of the Ca(2+)-dependent cell-cell adhesion molecule family, plays an essential role in the induction of the skeletal muscle differentiation programme. However, the molecular mechanisms which govern the formation of N-cadherin-dependent cell-cell contacts in myoblasts remain unexplored. RESULTS: In the present study, we show that N-cadherin-dependent cell contact formation in myoblasts is defined by two stages. In the first phase, N-cadherin is highly mobile in the lamellipodia extensions between the contacting cells. The second stage corresponds to the formation of mature N-cadherin-dependent cell contacts, characterized by the immobilization of a pool of N-cadherin which appears to be clustered in the interdigitated membrane structures that are also membrane attachment sites for F-actin filaments. We also demonstrated that the formation of N-cadherin-dependent cell-cell contacts requires a co-ordinated and sequential activity of Rac1 and RhoA. Rac1 is involved in the first stage and facilitates N-cadherin-dependent cell-cell contact formation, but it is not absolutely required. Conversely, RhoA is necessary for N-cadherin-dependent cell contact formation, since, via ROCK (Rho-associated kinase) signalling and myosin 2 activation, it allows the stabilization of N-cadherin at the cell-cell contact sites. CONCLUSIONS: We have shown that Rac1 and RhoA have opposite effects on N-cadherin-dependent cell-cell contact formation in C2C12 myoblasts and act sequentially to allow its formation.

Domaines: Biochimie, Biologie Moléculaire

Franck Comunale, Marie Causeret, Cyril Favard, Julien Cau, Nicolas Taulet, et al.. Rac1 and RhoA GTPases have antagonistic functions during N-cadherin-dependent cell-cell contact formation in C2C12 myoblasts.. Biology of the Cell, 2007, 99 (9), pp.503-17. ⟨10.1042/BC20070011⟩. ⟨hal-00216159⟩