Neuropilin in the midst of cell migration and retraction.

Neuropilin (NRP) is a 140 kDa membrane protein, with a large extracellular domain and a short cytoplasmic tail, that was isolated in 1987 from the optic tactum of Xenopus laevis. About 10 years after its isolation, NRP was identified as a receptor for semaphorin, a family of axonal chemorepellent proteins and for vascular endothelial growth factor (VEGF), a family of potent angiogenic factors. In the nervous system, NRP forms a high affinity semaphorin-binding complex with a receptor tyrosine kinase, plexin, that mediates semaphorin-induced growth cone collapse. On the endothelium, NRP is expressed together with KDR, a VEGF receptor tyrosine kinase. We have shown that NRP potentiated KDR-mediated endothelial cell migration and proliferation. Some tumor cells can express high levels of NRP, which is typically their only VEGF receptor, but do not seem to respond to VEGF directly. Possible use of NRP as a target for VEGF antagonists, in the context of antiangiogenic therapy, are described.