M-cadherin activates Rac1 GTPase through the Rho-GEF trio during myoblast fusion.
Cadherins are transmembrane glycoproteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion and play crucial role during skeletal myogenesis. M-cadherin is required for myoblast fusion into myotubes, but its mechanisms of action remain unknown. The goal of this study was to cast some light on the nature of the M-cadherin-mediated signals involved in myoblast fusion into myotubes. We found that the Rac1 GTPase activity is increased at the time of myoblast fusion and it is required for this process. Moreover, we showed that M-cadherin-dependent adhesion activates Rac1 and demonstrated the formation of a multiproteic complex containing M-cadherin, the Rho-GEF Trio, and Rac1 at the onset of myoblast fusion. Interestingly, Trio knockdown efficiently blocked both the increase in Rac1-GTP levels, observed after M-cadherin-dependent contact formation, and myoblast fusion. We conclude that M-cadherin-dependent adhesion can activate Rac1 via the Rho-GEF Trio at the time of myoblast fusion.
Charrasse
Sophie
S
Centre de Recherches de Biochimie Macromoléculaire, Centre National de la Recherche Scientifique, IFR 122, 34293 Montpellier, France.
Comunale
Franck
F
Fortier
Mathieu
M
Portales-Casamar
Elodie
E
Debant
Anne
A
Gauthier-Rouvière
Cécile
C
D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002448:Cell Adhesion; D002459:Cell Fusion; D002460:Cell Line; D004789:Enzyme Activation; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
D015820:Cadherins; D020662:Guanine Nucleotide Exchange Factors; D046912:Multiprotein Complexes; D009479:Neuropeptides; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; C490975:Trio protein, mouse; C070896:M-cadherin; D017346:Protein Serine-Threonine Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein