AbstractSemaphorins signal through Plexin receptors to mediate a range of predominantly repulsive effects on axons in the developing nervous system. Semaphorin-directed repulsive turning responses of cultured Xenopus neurons can be converted to attraction by manipulating cyclic nucleotide signaling pathways. cAMP- and cGMP-dependent response conversions are observed for many families of guidance cues, but a direct molecular link between guidance receptors and cyclic nucleotides has remained elusive. Recent findings indicate that the Drosophila A-kinase anchoring protein (AKAP) Nervy couples Plexin to PKA to modulate Semaphorin repulsion, suggesting a mechanism for the integration of diverse signaling inputs to the growth cone.