Neuropilins as Semaphorin receptors: in vivo functions in neuronal cell migration and axon guidance.

After the initial discovery of neuropilin-1 as an epitope on axons recognized by a monoclonal antibody, neuropilins were rediscovered in the search for receptors mediating the repulsive actions of class 3 Semaphorins, notably Sema3A. Neuropilins are the ligand binding moieties in the class 3 Semaphorin receptor complexes, with the signaling moieties apparently provided by members of the plexin family. In their capacity as Semaphorin receptors, neuropilins have been shown to transduce repulsive guidance signals that direct a large variety of cell migration and axon guidance events. We summarize their demonstrated roles in driving axon fasciculation, channeling various axonal populations, inhibiting axonal branching, creating exclusion zones for axons, and providing directional guidance cues by being presented in gradients. In addition to their roles in repulsive axon guidance, evidence is accumulating that neuropilins also transduce some attractive guidance functions of Semaphorins.