Function of Members of the Neuropilin Family as Essential Pleiotropic Cell Surface Receptors

The neuropilin (Nrp) family consists of essential multifunctional vertebrate cell surface receptors. Nrps were initially characterized as receptors for class III Semaphorin (Sema3) family members, functioning in axon guidance. Nips have also been shown to be critical for vascular endothelial growth factor-dependent angiogenesis. Intriguingly, recent data show that Nip function in these seemingly divergent pathways is critically determined by ligand-mediated cross-talk, which underlies Nip function in both physiological and pathological processes. In addition to functioning in these two pathways, Nips have been shown to specifically function in a number of other fundamental signaling pathways as Well. Multiple general mechanisms have been found to directly contribute to the pleiotropic function of Nip. Here we review critical general features of Nips that function as essential receptors integrating multiple molecular cues into diverse cellular signaling.