RRC ID 47960
著者 Sawaguchi S, Varshney S, Ogawa M, Sakaidani Y, Yagi H, Takeshita K, Murohara T, Kato K, Sundaram S, Stanley P, Okajima T.
タイトル O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals.
ジャーナル Elife
Abstract The glycosyltransferase EOGT transfers O-GlcNAc to a consensus site in epidermal growth factor-like (EGF) repeats of a limited number of secreted and membrane proteins, including Notch receptors. In EOGT-deficient cells, the binding of DLL1 and DLL4, but not JAG1, canonical Notch ligands was reduced, and ligand-induced Notch signaling was impaired. Mutagenesis of O-GlcNAc sites on NOTCH1 also resulted in decreased binding of DLL4. EOGT functions were investigated in retinal angiogenesis that depends on Notch signaling. Global or endothelial cell-specific deletion of Eogt resulted in defective retinal angiogenesis, with a mild phenotype similar to that caused by reduced Notch signaling in retina. Combined deficiency of different Notch1 mutant alleles exacerbated the abnormalities in Eogt-/- retina, and Notch target gene expression was decreased in Eogt-/-endothelial cells. Thus, O-GlcNAc on EGF repeats of Notch receptors mediates ligand-induced Notch signaling required in endothelial cells for optimal vascular development.
巻・号 6
公開日 2017-4-11
DOI 10.7554/eLife.24419
PII e24419
PMID 28395734
PMC PMC5388531
MeSH Acetylglucosamine / metabolism* Animals Cell Line Cricetinae Endothelial Cells / physiology Glycosylation* Humans Mice N-Acetylglucosaminyltransferases / metabolism* Neovascularization, Physiologic* Receptor, Notch1 / metabolism* Retina / physiology Signal Transduction*
IF 7.08
引用数 35
リソース情報
実験動物マウス RBRC01071 RBRC04495