Cell adhesion and Rho small GTPases

The Rho small GTPases, Cdc42, Rac1 and Rho, are implicated in regulation of integrin-mediated cell-substratum adhesion and cadherin-mediated cell-cell adhesion. Identification and characterization of effecters of these GTPases have provided insights into their modes of action. Rho-kinase, an effector of Rho, regulates integrin-mediated cell-substratum adhesion (focal adhesion) by regulating the phosphorylation state of myosin light chain (MLC): it directly phosphorylates MLC and also inactivates myosin phosphatase. IQGAP1, an effector of Cdc42 and Rac1, regulates cadherin-mediated cell-cell adhesion by interacting with β-catenin and dissociating α-catenin from the cadherin-catenins complex. Activated Cdc42 and Rac1 inhibit IQGAP1, thereby stabilizing the cadherin-catenins complex. Cdc42/Rac1 and IQGAP1 thus appear to constitute a switch that regulates cadherin-mediated cell-cell adhesion.