Syx, a RhoA guanine exchange factor, is essential for angiogenesis in Vivo. Circ Res 2008 Sep 26;103(7):710-6
Date
09/02/2008Pubmed ID
18757825Pubmed Central ID
PMC2758496DOI
10.1161/CIRCRESAHA.108.181388Scopus ID
2-s2.0-54449100292 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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 RAuthors
Keguo Li MD, PhD Research Scientist I in the Surgery department at Medical College of WisconsinRamani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCell 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
