The fate of the internalized apelin receptor is determined by different isoforms of apelin mediating differential interaction with β-arrestin
The fate of the internalized apelin receptor is determined by different isoforms of apelin mediating differential interaction with β-arrestin
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DOI：
10.1016/j.bbrc.2010.03.151
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发表时间：
2010-04-30
影响因子：
3.1
通讯作者：
O'Dowd, Brian F.
中科院分区：
文献类型：
--
作者：
Lee, Dennis K.;Ferguson, Stephen S. G.;O'Dowd, Brian F.
由apelin-13内化的apelin受体的特征是与β -阻滞蛋白解离并快速循环到细胞表面。矛盾的是，被apelin-36内化的apelin受体被隔离在细胞内。在apelin-13或apelin-36激活后，利用β -arrestin1和组成型活性和显性阴性Rab蛋白解决了参与apelin受体运输的特定途径。β -arrestin1与apelin-13内化受体分离，而apelin-36内化受体与β -arrestin1一起运输到细胞内区室。apelin-13内化受体通过rab4依赖机制迅速循环到细胞表面，而Rab7将受体靶向溶酶体。与显性阴性Rab4共表达的内化受体被转运到溶酶体中。这些观察结果揭示了一种新的配体依赖的apelin受体靶向β -阻滞蛋白相关和解离运输途径，以及不同的Rab蛋白在指导这些途径中的作用。(C) 2010爱思唯尔公司版权所有。
Internalization of the apelin receptor by apelin-13 is characterized by dissociation from beta-arrestins and rapid recycling to the cell surface. Paradoxically, the apelin receptor internalized by apelin-36 was sequestered intracellularly. The specific pathways involved in apelin receptor trafficking were resolved using beta-arrestin1 and constitutively active and dominant negative Rab proteins following activation by apelin-13 or apelin-36. beta-Arrestin1 dissociated from the apelin-13-internalized receptor while the apelin-36-internalized receptor was trafficked with beta-arrestin1 to intracellular compartments. The apelin-13-internalized receptor was rapidly recycled to the cell surface through a Rab4-dependent mechanism while Rab7 targeted the receptor to lysosomes. The internalized receptor co-expressed with dominant negative Rab4 were trafficked to lysosomes. These observations revealed a novel ligand-dependent targeting of the apelin receptor to beta-arrestin-associated and -dissociated trafficking pathways and a role for different Rab proteins to direct these pathways. (C) 2010 Elsevier Inc. All rights reserved.