Semaphorins command cells to move

Key Points Semaphorins are secreted or transmembrane proteins that mediate repulsive axon guidance, immune cell regulation, and vascular growth and remodelling. Semaphorins signal through plexins. Plexins, in turn, recruit and regulate kinases and Rho-family GTPases to control cell motility. It has recently been shown that plexins also have intrinsic GAP (GTPase-activating protein) activity towards R-Ras on semaphorin binding. Plexin GAP activity decreases the activity of R-Ras. Active R-Ras promotes integrin-mediated attachment to the extracellular matrix. Semaphorins have been shown in many systems to decrease integrin-mediated attachment. It is now possible to attribute these phenomena to the regulation of R-Ras through plexins. Semaphorins are secreted or transmembrane proteins that regulate cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumour progression. The main receptors for semaphorins are plexins, which have established roles in regulating Rho-family GTPases. Recent work shows that plexins can also influence R-Ras, which, in turn, can regulate integrins. Such regulation is probably a common feature of semaphorin signalling and contributes substantially to our understanding of semaphorin biology.