Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2.
Neuropilin-1 (NRP-1) is a type 1 membrane protein that binds the axon guidance factors belonging to the class-3 semaforin family. In endothelial cells, NRP-1 serves as a co-receptor for vascular endothelial growth factor (VEGF) and regulates VEGF receptor 2 (VEGFR-2)-dependent angiogenesis. Although gene-targeting studies documenting embryonic lethality in NRP-1 null mice have demonstrated a critical role for NRP-1 in vascular development, the activities of NRP-1 in mature endothelial cells have been incompletely defined. Using RNA interference-mediated silencing of NRP-1 or VEGFR-2 in primary human endothelial cells, we confirm that NRP-1 modulates VEGFR-2 signaling-dependent mitogenic functions of VEGF. Importantly, we now show that NRP-1 regulates endothelial cell adhesion to extracellular matrix proteins independently of VEGFR-2. Based on its dual role as an enhancer of VEGF activity and a mediator of endothelial cell adhesiveness described here, NRP-1 emerges as a promising molecular target for the development of antiangiogenic drugs.
Murga
Matilde
M
Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
Fernandez-Capetillo
Oscar
O
Tosato
Giovanna
G
D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000166:cytology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic; D039942:Neuropilin-1 / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000502:physiology*
D016326:Extracellular Matrix Proteins; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040301:Vascular Endothelial Growth Factor Receptor-2