Semaphorins are conserved signalling molecules that control a wide range of biological activities, including axonal guidance and cell migration. Activation of plexins, high-affinity receptors for semaphorins, inhibits integrin-mediated adhesion and cytoskeletal remodelling. Luca Tamagnone and colleagues now report that p190 Rho-GTPase activating protein (p190-RhoGAP) associates with plexins and is required for semaphorin signalling (see ). The authors show first that RhoA-GTP levels transiently decrease upon plexin activation in adherent cells. Given that p190-RhoGAP is a major downregulator of RhoA, the authors next investigated semaphorin signalling in p190-RhoGAP-deficient fibroblasts. They found that the functional activities mediated by plexins, such as cell collapse and inhibition of integrin function, were blocked or impaired in these cells but could be rescued by expression of exogenous p190-RhoGAP. Knocking down p190-RhoGAP by RNAi also blocked semaphorin signalling in epithelial cells, primary endothelial cells and neuroblasts. The authors therefore conclude that p190RhoGAP mediates semaphorin signalling to the actin cytoskeleton and to integrin-mediated adhesions through its interaction with plexins.
