Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration

Neuropilin 2 (NRP2) is a receptor for the vascular enclothelial growth factor (VEGF) and the sernaphorin (SEMA) families, 2 unrelated ligand families involved in angiogenesis and neuronal guidance. NRP2 specifically binds VEGF-A and VEGIF-C, although the biological relevance of these interactions in human endothelial cells is poorly understood. In this study, we show that both VEGF-A and VEGIF-C induce the interaction of NRP2 with VEGFR-2. This interaction correlated with an enhancement of the VEGIFIR-2 phosphorylation threshold. Overexpression of NRP2 in primary human enclothelial cells promoted cell survival induced by VEGF-A and VEGIF-C. In contrast, SEMA3F, another ligand for NRP2, was able to inhibit human enclothelial cell survival and migration induced by VEGIF-A and VEGF-C. Moreover, a siRINA targeting specifically NRP2 was a potent inhibitor of human enclothelial cell migration induced by VEGF-A and VEGIF-C. Thus, our data indicate that NlRP2 acts as a coreceptor that enhances human endothelial cell biological responses induced by VEGIF-A and VEGF-C.