N-cadherin/p120 catenin association at cell-cell contacts occurs in cholesterol-rich membrane domains and is required for RhoA activation and myogenesis.
p120 catenin is a major regulator of cadherin stability at cell-cell contacts and a modulator of Rho GTPase activities. In C2C12 myoblasts, N-cadherin is stabilized at cell contacts through its association with cholesterol-rich membrane domains or lipid rafts (LR) and acts as an adhesion-activated receptor that activates RhoA, an event required for myogenesis induction. Here, we report that association of p120 catenin with N-cadherin at cell contacts occurs specifically in LR. We demonstrate that interaction of p120 catenin with N-cadherin is required for N-cadherin association with LR and for its stabilization at cell contacts. LR disruption inhibits myogenesis induction and N-cadherin-dependent RhoA activation as does the perturbation of the N-cadherin-p120 catenin complex after p120 catenin knockdown. Finally, we observe an N-cadherin-dependent accumulation of RhoA at phosphatidylinositol 4,5-bisphosphate-enriched cell contacts which is lost after LR disruption. Thus, a functional N-cadherin-catenin complex occurs in cholesterol-rich membrane microdomains which allows the recruitment of RhoA and the regulation of its activity during myogenesis induction.
Taulet
Nicolas
N
Centre de Recherche de Biochimie Macromoléculaire, Universités Montpellier 2 et 1, CNRS, Uníté Mixte de Recherche 5237, Institut Fédératif de Recherche 122, 1919 Route de Mende, 34293 Montpellier, France.
Comunale
Franck
F
Favard
Cyril
C
Charrasse
Sophie
S
Bodin
Stéphane
S
Gauthier-Rouvière
Cécile
C
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry*; D036681:Fluorescence Recovery After Photobleaching; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D002784:Cholesterol; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse