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 opt ic tactum of Xenopus laevis. About 10 years after its isolation, NRP was id entified as a receptor for semaphorin, a family of axonal chemorepellent pr oteins and for vascular endothelial growth factor (VEGF), a family of poten t angiogenic factors. In the nervous system, NRP forms a high affinity sema phorin-binding complex with a receptor tyrosine kinase, plexin, that mediat es semaphorin-induced growth cone collapse. On the endothelium, NRP is expr essed together with KDR, a VEGF receptor tyrosine kinase. We have shown tha t 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 antiangiogen ic therapy, are described. (C) 2001 Elsevier Science Ltd. All rights reserv ed.