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 |