論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01071 RBRC04495 |