|ZFIN ID: ZDB-PUB-150207-2|
CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development
Tu, T., Zhang, C., Yan, H., Luo, Y., Kong, R., Wen, P., Ye, Z., Chen, J., Feng, J., Liu, F., Wu, J.Y., Yan, X.
|Source:||Cell Research 25(3): 275-87 (Journal)|
|Registered Authors:||Liu, Feng, Zhang, Chunxia|
|PubMed:||25656845 Full text @ Cell Res.|
Tu, T., Zhang, C., Yan, H., Luo, Y., Kong, R., Wen, P., Ye, Z., Chen, J., Feng, J., Liu, F., Wu, J.Y., Yan, X. (2015) CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development. Cell Research. 25(3):275-87.
ABSTRACTAngiogenesis, 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.Cell Research advance online publication 6 February 2015; doi:10.1038/cr.2015.15.