Semaphorin Signaling Meets Rap

Plexins are transmembrane receptors for semaphorins that serve as guidance cues for neurite outgrowth. The intracellular region of plexins contains a guanosine triphosphatase (GTPase)–activating protein (GAP) domain for Ras. New evidence shows that the GAP activity is specific for Rap proteins, small GTPases involved in the regulation of processes that are potentially important for axon guidance, including cell adhesion and migration. Semaphorin-induced dimerization stimulates plexin GAP activity, thereby locally inhibiting Rap1 and enabling neurite retraction. This important finding connects semaphorin signaling to Rap-mediated signaling and is another intriguing example of how small GTPases are used for spatial and temporal control of cell behavior.