Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Biochem Biophys Res Commun. 2010 Apr 30;395(2):185-9. doi: 10.1016/j.bbrc.2010.03.151. Epub 2010 Mar 28.
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.
内吞化的阿片肽受体通过阿片肽 -13 的特点是从β-arrestin 解离和快速循环到细胞表面。矛盾的是，阿片肽 -36 内吞化的阿片肽受体被隔离在细胞内。使用β-arrestin1 和组成性激活和显性负性 Rab 蛋白解决了涉及阿片肽受体运输的特定途径，在激活阿片肽 -13 或阿片肽 -36 后。β-arrestin1 从阿片肽 -13 内化的受体解离，而阿片肽 -36 内化的受体与β-arrestin1 一起运输到细胞内隔室。阿片肽 -13 内化的受体通过 Rab4 依赖性机制快速循环到细胞表面，而 Rab7 将受体靶向溶酶体。与显性负性 Rab4 共表达的内化受体被运输到溶酶体。这些观察结果揭示了一种新的配体依赖性靶向阿片肽受体的β-arrestin 相关和 - 解离运输途径，以及不同 Rab 蛋白在指导这些途径中的作用。
