Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase
Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase
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DOI：
10.1016/j.cellsig.2008.01.014
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发表时间：
2008-06-01
影响因子：
4.8
通讯作者：
Wu, Guangyu
中科院分区：
文献类型：
--
作者：
Dong, Chunmin;Zhou, Fuguo;Wu, Guangyu
G蛋白偶联受体(GPCRs)从内质网(ER)输出的分子机制目前仍不清楚。在这篇论文中，我们研究了Sar1 GTPase在α(2B)-肾上腺素能(α(2B)-AR)、β(2)-AR和血管紧张素II 1型受体(AT1R)的细胞表面靶向、信号传递和ER输出中的作用。Sar1 GTP酶协调COPII包裹的囊泡的组装和萌发。GTP结合突变体Sar1H79G显著抑制细胞表面α(2B)-AR、β(2)-AR和AT1R的表达以及受体介导的ERK1/2激活，提示这些受体的输出是通过Sar1依赖的COPII包被囊泡介导的。有趣的是，亚细胞分布分析表明，在表达Sar1H79G的细胞中，α(2B)-AR和ATIR高度集中在靠近细胞核的离散位置，而β(2)-AR则呈ER分布。这些数据表明，Sar1催化的有效GTP水解对肾上腺素能和血管紧张素11受体的ER输出有不同的调节作用。这些数据提供了第一个证据，表明不同的GPCR募集到内质网膜上的COPII小泡中的不同机制。(C)2008 Elsevier Inc.保留所有权利。
The molecular mechanism underlying the export of G protein-coupled receptors (GPCRs) from the endoplasmic reticulum (ER) remains largely unknown. In this manuscript, we investigated the role of Sar1 GTPase, which coordinates the assembly and budding of COPII-coated vesicles, in the cell-surface targeting, signaling and ER export Of alpha(2B)-adrenergic (alpha(2B)-AR), beta(2)-AR and angiotensin II type 1 receptors (AT1R). The cell-surface expression of alpha(2B)-AR, beta(2)-AR and AT1R, and receptor-mediated ERK1/2 activation were significantly attenuated by the GTP-bound mutant Sar1H79G, suggesting that export from the ER of these receptors is mediated through the Sar1-dependent COPII-coated vesicles. Interestingly, subcellular distribution analyses showed that alpha(2B)-AR and ATIR were highly concentrated at discrete locations near the nucleus in cells expressing Sar1H79G, whereas beta(2)-AR exhibited an ER distribution. These data indicate that Sar1-catalyzed efficient GTP hydrolysis differentially regulates ER export of adrenergic and angiotensin 11 receptors. These data provide the first evidence indicating distinct mechanisms for the recruitment of different GPCRs into the COPII vesicles on the ER membrane. (C) 2008 Elsevier Inc. All rights reserved.