G-Protein-Coupled Receptor-2-Interacting Protein-1 Controls Stalk Cell Fate by Inhibiting Delta-like 4-Notch1 Signaling.
G-Protein-Coupled Receptor-2-Interacting Protein-1 Controls Stalk Cell Fate by Inhibiting Delta-like 4-Notch1 Signaling.
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DOI：
10.1016/j.celrep.2016.11.017
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发表时间：
2016-12-06
期刊：
影响因子：
8.8
通讯作者：
Pang J
中科院分区：
文献类型：
--
作者：
Majumder S;Zhu G;Xu X;Senchanthisai S;Jiang D;Liu H;Xue C;Wang X;Coia H;Cui Z;Smolock EM;Libby RT;Berk BC;Pang J
Dll 4的时空定位和表达对于出芽血管生成是至关重要的。然而，相关机制知之甚少。在这里，我们表明，G-蛋白偶联受体激酶相互作用蛋白-1（GIT 1）是一个强大的内源性抑制剂Dll 4-Notch 1信号，专门控制茎细胞的命运。GIT 1在茎细胞中高度表达，但在茎尖细胞中不表达。GIT 1缺陷显著增强Dll 4表达和Notch 1信号传导，导致受损的视网膜出芽血管生成，这可以通过用Notch抑制剂或Dll 4中和抗体治疗来挽救。Notch 1通过高度保守的锚蛋白（ANK）重复结构域与重组无毛结合蛋白抑制因子（RBP-J，Notch的转录调节因子）结合来调节Dll 4的表达。我们发现，GIT 1，其中也包含一个ANK结构域，抑制Notch 1-Dll 4信号通路与Notch 1 ANK结构域竞争结合RBP-J柄细胞。
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor, or Dll4 neutralizing antibody. Notch1 regulates Dll4 expression by binding to recombining binding protein suppressor of hairless (RBP-J, a transcriptional regulator of Notch) via a highly conserved ankyrin (ANK) repeat domain. We show that GIT1, which also contains an ANK domain, inhibits the Notch1-Dll4 signaling pathway by competing with Notch1 ANK domain for binding to RBP-J in stalk cells.
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影响因子：
10.5
作者：
Ruhrberg, C;Gerhardt, H;Shima, DT
通讯作者：
Shima, DT
影响因子：
20.3
作者：
Trindade, Alexandre;Kumar, S. Ram;Duarte, Antonio
通讯作者：
Duarte, Antonio
DOI：
10.1073/pnas.0611177104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Suchting, Steven;Freitas, Catarina;Eichmann, Anne
通讯作者：
Eichmann, Anne
影响因子：
4.8
作者：
Caolo, Vincenza;van den Akker, Nynke M. S.;Molin, Daniel G. M.
通讯作者：
Molin, Daniel G. M.
影响因子：
3.1
作者：
Harrington, Laura S.;Sainson, Richard C. A.;Harris, Adrian L.
通讯作者：
Harris, Adrian L.