The transmembrane protein off-track associates with plexins and functions downstream of semaphorin signaling during axon guidance

The Plexin family of transmembrane proteins appears to function as repulsiv e receptors for most if not all Semaphorins. Here, we use genetic and bioch emical analysis in Drosophila to show that the transmembrane protein Off-tr ack (OTK) associates with Plexin A, the receptor for Sema 1a, and that OTK is a component of the repulsive signaling response to Semaphorin ligands. I n vitro, OTK associates with Plexins. In vivo, mutations in the otk gene le ad to phenotypes resembling those of loss-of-function mutations of either S ema1a or PlexA. The otk gene displays strong genetic interactions with Sema 1a and PlexA, suggesting that OTK and Plexin A function downstream of Sema 1a.