PUBLICATION

CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development

Authors
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.
ID
ZDB-PUB-150207-2
Date
2015
Source
Cell Research   25(3): 275-87 (Journal)
Registered Authors
Liu, Feng, Zhang, Chunxia
Keywords
none
MeSH Terms
  • Animals
  • CD146 Antigen/genetics
  • CD146 Antigen/metabolism
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells/physiology
  • Humans
  • Mice
  • Mice, Transgenic
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology*
  • Nerve Growth Factors/genetics
  • Nerve Growth Factors/metabolism*
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Cell Surface/genetics
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Vascular Endothelial Growth Factor Receptor-2/metabolism
  • Zebrafish
PubMed
25656845 Full text @ Cell Res.
Abstract
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.Cell Research advance online publication 6 February 2015; doi:10.1038/cr.2015.15.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes