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 endothelial growth factor (VEGF) and the semaphorin (SEMA) families, 2 unrelated ligand families involved in angiogenesis and neuronal guidance. NRP2 specifically binds VEGF-A and VEGF-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 VEGF-C induce the interaction of NRP2 with VEGFR-2. This interaction correlated with an enhancement of the VEGFR-2 phosphorylation threshold. Overexpression of NRP2 in primary human endothelial cells promoted cell survival induced by VEGF-A and VEGF-C. In contrast, SEMA3F, another ligand for NRP2, was able to inhibit human endothelial cell survival and migration induced by VEGF-A and VEGF-C. Moreover, a siRNA targeting specifically NRP2 was a potent inhibitor of human endothelial cell migration induced by VEGF-A and VEGF-C. Thus, our data indicate that NRP2 acts as a coreceptor that enhances human endothelial cell biological responses induced by VEGF-A and VEGF-C.
Favier
Benoit
B
Angiogenesis and Thrombosis Department, Sanofi-Synthelabo Research, 31036 Toulouse, France.
Alam
Antoine
A
Barron
Pauline
P
Bonnin
Jacques
J
Laboudie
Patricia
P
Fons
Pierre
P
Mandron
Marie
M
Herault
Jean-Pascal
JP
Neufeld
Gera
G
Savi
Pierre
P
Herbert
Jean-Marc
JM
Bono
Françoise
F
D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D039943:Neuropilin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; D034741:RNA, Small Interfering; C491230:SEMA3F protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3