Syx, a rhoA guanine exchange factor, is essential for angiogenesis in vivo

Maija K. Garnaas, Karen L. Moodie, Miao Liang Liu, Ganesh V. Samant, Keguo Li, Ruth Marx, Jay M. Baraban, Arie Horowitz, Ramani Ramchandran

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)710-716
Number of pages7
JournalCirculation research
Volume103
Issue number7
DOIs
StatePublished - Sep 26 2008

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Keywords

  • Intersomitic vessels
  • Knockdown
  • PDZ
  • Vascular
  • Zebrafish

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Garnaas, M. K., Moodie, K. L., Liu, M. L., Samant, G. V., Li, K., Marx, R., Baraban, J. M., Horowitz, A., & Ramchandran, R. (2008). Syx, a rhoA guanine exchange factor, is essential for angiogenesis in vivo. Circulation research, 103(7), 710-716. https://doi.org/10.1161/CIRCRESAHA.108.181388