摘要: Angiogenesis, a process that newly-formed blood vessels sprout from pre-existing ones, is vital for vertebrate development and adult homeostasis. Previous studies have demonstrated that the neuronal guidance molecule netrin-1 participates in angiogenesis and morphogenesis of the vascular system. Netrin-1 exhibits dual activities in angiogenesis: either promoting or inhibiting angiogenesis. The anti-angiogenic activity of netrin-1 is mediated by UNC5B receptor. However, how netrin-1 promotes angiogenesis remained unclear. Here we report that CD146, an endothelial transmembrane protein of the immunoglobulin superfamily, is a receptor for netrin-1. Netrin-1 binds to CD146 with high affinity, inducing endothelial cell activation and downstream signaling in a CD146-dependent manner. Conditional knockout of the cd146 gene in the murine endothelium or disruption of netrin-CD146 interaction by a specific anti-CD146 antibody blocks or reduces netrin-1-induced angiogenesis. In zebrafish embryos, downregulating either netrin-1a or CD146 results in vascular defects with striking similarity. Moreover, knocking down CD146 blocks ectopic vascular sprouting induced by netrin-1 overexpression. Together, our data uncover CD146 as a previously unknown receptor for netrin-1 and also reveal a functional ligand for CD146 in angiogenesis, demonstrating the involvement of netrin-CD146 signaling in angiogenesis during vertebrate development.
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期刊:
CELL RESEARCH
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分类:
生物学
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生物物理学
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细胞生物学
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引用:
ChinaXiv:201605.01203
(或此版本
ChinaXiv:201605.01203V1)
DOI:10.12074/201605.01203V1
CSTR:32003.36.ChinaXiv.201605.01203.V1
- 推荐引用方式:
Tu, Tao,Yan, Huiwen,Luo, Yongting,Ye, Zhongde,Chen, Jianan,Feng, Jing,Yan, Xiyun,Zhang, Chunxia,Liu, Feng,Kong, Ruirui,Wen, Pushuai,Wu, Jane Y.,Wu, Jane Y..(2016).CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development.CELL RESEARCH.[ChinaXiv:201605.01203]
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