Myosin 2 Is a Key Rho Kinase Target Necessary for the Local Concentration of E-Cadherin at Cell–Cell Contacts

Abstract

Classical cadherins accumulate at cell–cell contacts as a characteristic response to productive adhesive ligation. Such local accumulation of cadherins is a developmentally regulated process that supports cell adhesiveness and cell–cell cohesion. Yet the molecular effectors responsible for cadherin accumulation remain incompletely understood. We now report that Myosin 2 is critical for cells to concentrate E-cadherin at cell–cell contacts. Myosin 2 is found at cadherin-based cell–cell contacts and its recruitment requires E-cadherin activity. Indeed, both Myosin 2 recruitment and its activation were stimulated by E-cadherin homophilic ligation alone. Inhibition of Myosin 2 activity by blebbistatin or ML-7 rapidly impaired the ability of cells to concentrate E-cadherin at adhesive contacts, accompanied by decreased cadherin-based cell adhesiveness. The total surface expression of cadherins was unaffected, suggesting that Myosin 2 principally regulates the regional distribution of cadherins at the cell surface. The recruitment of Myosin 2 to cadherin contacts, and its activation, required Rho kinase; furthermore, inhibition of Rho kinase signaling effectively phenocopied the effects of Myosin 2 inhibition. We propose that Myosin 2 is a key effector of Rho-Rho kinase signaling that regulates cell–cell adhesion by determining the ability of cells to concentrate cadherins at contacts in response to homophilic ligation.