New insights into the interaction between the semaphoring receptor plexin B1 and the small GTPases of the Rho family

Small GTPases of the Ras and Rho families as well as the transmembrane semaphorin receptor/plexin family play a critical role in axonal guidance, the immune response, cell migration and tumor growth. To date the relationship between the semaphorin receptors/plexins and small GTPases is unclear. The architecture of the cytoplasmic domain of the plexins contains two remarkable features: (i) a middle segment (200 amino acid) called GTPase-binding domain (GBD) that may be responsible for the binding of the small GTPases of the Rho family (e.g. Rac1, Rnd1) and (ii) a N-terminal (170 amino acid) and a C-terminal (180 amino acid) segments interrupted by the GBD-domain show high sequence identity to the Ras-specific GTPase-activating proteins (RasGAPs). These segments have been shown for plexin B1 to be a functional GAP for the Ras-related protein R-Ras1. In order to understand the role of plexin B1 interaction with small GTPases und to gain insight into the mechanism of the RBD and the GAP functions we purified various plexins and analyzed comprehensively their interaction with various members of the Ras and Rho family. We identified a large number of GTPases interacting with the RBD but could not verify the GAP activity of the plexin B1 on Ras proteins as described before.