Syx, a RhoA Guanine Exchange Factor, Is Essential for Angiogenesis in Vivo

Circ Res. 2008 Sep 26;103(7):710-6. doi: 10.1161/CIRCRESAHA.108.181388. Epub 2008 Aug 28.

Abstract

Rho GTPases play an important and versatile role in several biological processes. In this study, we identified the zebrafish ortholog of the mammalian Rho A guanine exchange factor, synectin-binding guanine exchange factor (Syx), and determined its in vivo function in the zebrafish and the mouse. We found that Syx is expressed specifically in the vasculature of these organisms. Loss-of-function studies in the zebrafish and mouse point to a specific role for Syx in angiogenic sprouting in the developing vascular bed. Importantly, vasculogenesis and angioblast differentiation steps were unaffected in syx knockdown zebrafish embryos, and the vascular sprouting defects were partially rescued by the mouse ortholog. Syx knockdown in vitro impairs vascular endothelial growth factor-A-induced endothelial cell migration and angiogenesis. We have also uncovered a potential mechanism of endothelial sprout guidance in which angiomotin, a component of endothelial cell junctions, plays an additive role with Syx in directing endothelial sprouts. These results identify Syx as an essential contributor to angiogenesis in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Intercellular Junctions / genetics
  • Intercellular Junctions / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Neovascularization, Physiologic*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Amot protein, mouse
  • Guanine Nucleotide Exchange Factors
  • Intercellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Syx protein, mouse
  • Vascular Endothelial Growth Factor A
  • Zebrafish Proteins
  • plekhg5a protein, zebrafish
  • vascular endothelial growth factor A, mouse
  • rhoA GTP-Binding Protein