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Syx, a RhoA guanine exchange factor, is essential for angiogenesis in Vivo. Circ Res 2008 Sep 26;103(7):710-6

Date

09/02/2008

Pubmed ID

18757825

Pubmed Central ID

PMC2758496

DOI

10.1161/CIRCRESAHA.108.181388

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.

Author List

Garnaas MK, Moodie KL, Liu ML, Samant GV, Li K, Marx R, Baraban JM, Horowitz A, Ramchandran R

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Movement
Endothelial Cells
Guanine Nucleotide Exchange Factors
Intercellular Junctions
Intercellular Signaling Peptides and Proteins
Mice
Microfilament Proteins
Neovascularization, Physiologic
Vascular Endothelial Growth Factor A
Zebrafish
Zebrafish Proteins
rhoA GTP-Binding Protein
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d