Neuropilin-1 binds to VEGF121 and regulates endothelial cell migration and sprouting
Neuropilin-1 binds to VEGF121 and regulates endothelial cell migration and sprouting
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DOI：
10.1074/jbc.m703554200
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发表时间：
2007-08-17
影响因子：
4.8
通讯作者：
Watts, Ryan J.
中科院分区：
文献类型：
--
作者：
Pan, Qi;Chathery, Yvan;Watts, Ryan J.
神经纤毛蛋白-1（NRP 1）首先被描述为轴突导向分子Semaphorin 3A的受体，调节神经系统的发育。后来证明NRP 1是血管内皮生长因子（VEGF），特别是VEGF的同种型特异性受体（165）.许多兴趣已放在血管生物学中的各种VEGF亚型的作用。在这里，我们报告说，阻断NRP 1功能，使用最近描述的抗体，抑制VEGF（165）结合NRP 1，令人惊讶地减少VEGF（121）诱导的迁移和芽形成的内皮细胞。受此观察结果的启发，进行了NRP 1与各种VEGF同种型的直接结合研究。我们发现VEGF（121）直接与NRP 1结合;然而，与VEGF 165不同，VEGF（121）不足以桥接NRP 1中心点VEGFR 2复合物。此外，我们发现VEGFR 2增强VEGF（165），但不增强VEGF（121）与NRP 1的结合。我们提出了一个新的模型NRP 1与各种VEGF亚型的相互作用。
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 VEGF165, VEGF(121) is not sufficient to bridge the NRP1 center dot 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.