Neuropilin-1 binds to VEGF121 and regulates endothelial cell migration and sprouting.
Neuropilin-1 (NRP1) was first described as a receptor for the axon guidance molecule, Semaphorin3A, regulating the development of the nervous system. It was later shown that NRP1 is an isoform-specific receptor for vascular endothelial growth factor (VEGF), specifically VEGF(165). Much interest has been placed on the role of the various VEGF isoforms in vascular biology. Here we report that blocking NRP1 function, using a recently described antibody that inhibits VEGF(165) binding to NRP1, surprisingly reduces VEGF(121)-induced migration and sprout formation of endothelial cells. Intrigued by this observation, direct binding studies of NRP1 to various VEGF isoforms were performed. We show that VEGF(121) binds directly to NRP1; however, unlike VEGF(165), VEGF(121) is not sufficient to bridge the NRP1.VEGFR2 complex. Additionally, we show that VEGFR2 enhances VEGF(165), but not VEGF(121) binding to NRP1. We propose a new model for NRP1 interactions with various VEGF isoforms.
Pan
Qi
Q
Department of Tumor Biology, Genentech, Inc., South San Francisco, California 94080, USA.
Chathery
Yvan
Y
Wu
Yan
Y
Rathore
Nisha
N
Tong
Raymond K
RK
Peale
Franklin
F
Bagri
Anil
A
Tessier-Lavigne
Marc
M
Koch
Alexander W
AW
Watts
Ryan J
RJ
D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D039942:Neuropilin-1 / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism / Q000502:physiology
D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040301:Vascular Endothelial Growth Factor Receptor-2