• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >ARF6 regulates angiotensin II type 1 receptor endocytosis by controlling the recruitment of AP-2 and clathrin
【24h】

ARF6 regulates angiotensin II type 1 receptor endocytosis by controlling the recruitment of AP-2 and clathrin

机译：ARF6通过控制AP-2和网格蛋白的募集来调节血管紧张素II 1型受体的内吞作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We have previously shown that the ADP-ribosylation factor 6 (ARF6), a small GTP-binding protein, is important for the internalization of several G protein-coupled receptors. Here, we propose to elucidate the molecular steps controlled by ARF6 in the endocytic process of the angiotensin II type I receptor (ATR), a model receptor being internalized via the clathrin-coated vesicle pathway. In HEK 293 cells, angiotensin II stimulation leads to the formation of a complex including ARF6, the beta-subunit of AP-2 and the heavy chain of clathrin. In vitro experiments indicate that the interactions between ARF6 and the beta-subunit of AP-2 as well as with the heavy chain of clathrin are direct, and dependent upon the nature of the nucleotide bound to ARF6. beta 2-adaptin binds to ARF6-GDP while clathrin preferentially interacts with ARF6 when loaded with GTP. These interactions have an important physiological consequence. Indeed, depletion of ARF6 prevents the agonist-dependent recruitment of beta 2-adaptin and clathrin to the activated ATR. Interestingly, in these cells, the plasma membrane redistribution of either beta 2-adaptin-GFP or beta arrestin 2-GFP. following Ang II stimulation, is altered. Both proteins are defective in clustering into large punctated structure at the plasma membrane compared to control conditions. Taken together, these results suggest that the cycling of ARF6 between its GDP-and GTP-bound states coordinates the recruitment of AP-2 and clathrin to activated receptors during the endocytic process. (C) 2007 Elsevier Inc. All rights reserved.
机译：我们以前已经表明，ADP-核糖基化因子6（ARF6），一种小的GTP结合蛋白，对于几种G蛋白偶联受体的内在化很重要。在这里，我们建议阐明血管紧张素II型I受体（ATR）的内吞过程中由ARF6控制的分子步骤，该模型受体通过网格蛋白包被的囊泡途径被内化。在HEK 293细胞中，血管紧张素II刺激导致形成复合物，包括ARF6，AP-2的β亚基和网格蛋白的重链。体外实验表明，ARF6与AP-2的β亚基之间以及与网格蛋白的重链之间的相互作用是直接的，并且取决于与ARF6结合的核苷酸的性质。 β2-adaptin与ARF6-GDP结合，而网格蛋白在加载GTP时优先与ARF6相互作用。这些相互作用具有重要的生理后果。确实，ARF6的消耗阻止了激动剂依赖的β2-适配蛋白和网格蛋白向活化的ATR募集。有趣的是，在这些细胞中，β2-adaptin-GFP或β抑制蛋白2-GFP的质膜重新分布。 Ang II刺激后，被改变。与对照条件相比，这两种蛋白在质膜上都聚集成大的点状结构是有缺陷的。两者合计，这些结果表明，ARF6在其GDP和GTP结合状态之间的循环协调了内吞过程中AP-2和网格蛋白向活化受体的募集。 （C）2007 Elsevier Inc.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号