Published online before print May 7, 2009, doi: 10.1161/CIRCRESAHA.108.191718
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Submitted on November 25, 2008
Revised on April 27, 2009
Accepted on April 28, 2009
Genetic Evidence for a Noncanonical Function of Seryl-tRNA Synthetase in Vascular Development
Wiebke Herzog ;
From the Department of Biochemistry and Biophysics and the Cardiovascular Research Institute (W.H., J.H., D.Y.R.S.), Programs in Developmental Biology, Genetics, and Human Genetics, University of California San Francisco, Westphalian Wilhelms University and Max-Planck Institute for Molecular Biomedicine (W.H., K.M.), Muenster, Germany.
* To whom correspondence should be addressed. E-mail: didier.stainier{at}ucsf.edu.
In a recent genetic screen, we identified mutations in genes important for vascular development and maintenance in zebrafish (Jin et al. Dev Biol. 2007;307:29–42). 32 Mutations at the adrasteia (adr) locus cause a pronounced dilatation of the aortic arch vessels as well as aberrant patterning of the hindbrain capillaries and, to a lesser extent, intersomitic vessels. This dilatation of the aortic arch vessels does not appear to be caused by increased cell proliferation but is dependent on vascular endothelial growth factor (Vegf) signaling. By positional cloning, we isolated seryl-tRNA synthetase (sars) as the gene affected by the adr mutations. Small interfering RNA knockdown experiments in human umbilical vein endothelial cell cultures indicate that SARS also regulates endothelial sprouting. These analyses of zebrafish and human endothelial cells reveal a new noncanonical function of Sars in endothelial development.
Key words: aminoacyl-tRNA synthetases • seryl-tRNA synthetase • Sars • SerRS • zebrafish • angiogenesis • vascular dilatation