N-cadherin-dependent cell-cell contact regulates Rho GTPases and beta-catenin localization in mouse C2C12 myoblasts.
N-cadherin, a member of the Ca(2+)-dependent cell-cell adhesion molecule family, plays an essential role in skeletal muscle cell differentiation. We show that inhibition of N-cadherin-dependent adhesion impairs the upregulation of the two cyclin-dependent kinase inhibitors p21 and p27, the expression of the muscle-specific genes myogenin and troponin T, and C2C12 myoblast fusion. To determine the nature of N-cadherin-mediated signals involved in myogenesis, we investigated whether N-cadherin-dependent adhesion regulates the activity of Rac1, Cdc42Hs, and RhoA. N-cadherin-dependent adhesion decreases Rac1 and Cdc42Hs activity, and as a consequence, c-jun NH2-terminal kinase (JNK) MAPK activity but not that of the p38 MAPK pathway. On the other hand, N-cadherin-mediated adhesion increases RhoA activity and activates three skeletal muscle-specific promoters. Furthermore, RhoA activity is required for beta-catenin accumulation at cell-cell contact sites. We propose that cell-cell contacts formed via N-cadherin trigger signaling events that promote the commitment to myogenesis through the positive regulation of RhoA and negative regulation of Rac1, Cdc42Hs, and JNK activities.
Charrasse
Sophie
S
Centre de Recherche de Biochimie Macromoléculaire, 34293 Montpellier Cedex, France.
Meriane
Mayya
M
Comunale
Franck
F
Blangy
Anne
A
Gauthier-Rouvière
Cécile
C
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; C081345:Cdc42Hs-associated kinase; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein