Neuropilin-1 enforces extracellular matrix signalling via ABL1 to promote angiogenesis

Biochem Soc Trans. 2014 Oct;42(5):1429-34. doi: 10.1042/BST20140141.

Abstract

Neuropilin-1 (NRP1), together with neuropilin-2, belongs to the neuropilin family. Neuropilins are transmembrane proteins essential for vascular and neural development and act as co-receptors for secreted signalling molecules of the class 3 semaphorin and vascular endothelial growth factor A (VEGF-A) families. NRP1 promotes VEGF-A signal in blood vascular endothelium and semaphorin signal in lymphatic endothelium, by forming complexes with its co-receptors. Mouse mutant studies established that NRP1 expression is essential during development because mice lacking NRP1 expression die embryonically and show severe neuronal and cardiovascular defects. Even though the contribution of NRP1 to vascular development has been mainly ascribed to its function as a VEGF-A receptor, recent evidence suggests that NRP1 contributes to angiogenesis through VEGF-independent mechanisms. In the present paper, we provide an overview of NRP1 functions in the vasculature and discuss current knowledge of NRP1-dependent signalling in the endothelium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Extracellular Matrix*
  • Humans
  • Mice, Mutant Strains
  • Models, Biological*
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic*
  • Neuropilin-1 / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / agonists
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins c-abl