Cell adhesion and Rho small GTPases

The Rho small GTPases, Cdc42, Ra1 and Rho, are implicated in regulation of integrin-mediated cell-substratum adhesion and cadherin-mediated cell-cell adhesion. Identification and characterization of effectors of these GTPases have provided insights into their modes of action. Rho-kinase, an effector of Rho, regulates integrin-mediated cell-substratum adhesion (focal adhesi on) by regulating the phosphorylation state of myosin light chain (MLC): it directly phosphorylates MLC and also inactivates myosin phosphatase, IQGAP 1, an effector of Cdc42 and Ra1, regulates cadherin-mediated cell-cell adhe sion by interacting with beta-catenin and dissociating alpha-catenin from t he cadherin-catenins complex. Activated Cdc4.2 and Rad inhibit IQGAP1, ther eby stabilizing the cadherin-catenins complex. Cdc42/Rac1 and IQGAP1 thus a ppear to constitute a switch that regulates cadherin-mediated cell-cell adh esion.