title: Rac1 and RhoA GTPases have antagonistic functions during N-cadherin-dependent cell-cell contact formation in C2C12 myoblasts.
abstract: BACKGROUND
  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.
authors: CRBM, CNRS, 1919 Route de Mende, 34293 Montpellier, France.
authors: Franck
authors: F
authors: Comunale
authors: Marie
authors: M
authors: Causeret
authors: Cyril
authors: C
authors: Favard
authors: Julien
authors: J
authors: Cau
authors: Nicolas
authors: N
authors: Taulet
authors: Sophie
authors: S
authors: Charrasse
authors: Cécile
authors: C
authors: Gauthier-Rouvière
mesh_terms: D015820:Cadherins / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D032446:Myoblasts / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: D015820:Cadherins; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein