A transplantable sorting signal that is sufficient to mediate rapid recycling of G protein-coupled receptors
A transplantable sorting signal that is sufficient to mediate rapid recycling of G protein-coupled receptors
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DOI：
10.1074/jbc.m107417200
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发表时间：
2001-11-30
影响因子：
4.8
通讯作者：
von Zastrow, M
中科院分区：
文献类型：
--
作者：
Gage, RM;Kim, KA;von Zastrow, M
β (2)-肾上腺素能受体和 δ 阿片受体代表不同的 G 蛋白偶联受体，它们通过网格蛋白包被的凹坑进行激动剂诱导的内吞作用，但在回收和降解膜途径之间的内吞后分类方面分别存在显着差异。先前的结果表明，β(2)-肾上腺素能受体羧基末端胞质结构域的远端部分参与 PDZ 结构域介导的蛋白质相互作用，是激动剂诱导的内吞作用后受体有效回收所必需的。在这里，我们证明，包含该蛋白质相互作用结构域核心的四残基序列（DSLL）充当可移植的内吞分选信号，足以将内吞的δ阿片受体重新路由到快速循环途径，抑制受体的蛋白水解下调，并在相同细胞中共表达时介导来自野生型等位基因的突变受体的受体自主分选。这些观察结果定义了介导异源 G 蛋白偶联受体快速回收的可移植信号，并且它们表明某些膜蛋白的快速回收不是通过大量膜流发生的，而是由特定的内吞分选机制介导的。
The beta (2)-adrenergic receptor and delta opioid receptor represent distinct G protein-coupled receptors that undergo agonist-induced endocytosis via clathrin-coated pits but differ significantly in their postendocytic sorting between recycling and degradative membrane pathways, respectively. Previous results indicate that a distal portion of the carboxyl-terminal cytoplasmic domain of the beta (2)-adrenergic receptor, which engages in PDZ domain-mediated protein interaction, is required for efficient recycling of receptors after agonist-induced endocytosis. Here we demonstrate that a four-residue sequence (DSLL) comprising the core of this protein interaction domain functions as a transplantable endocytic sorting signal that is sufficient to re-route endocytosed delta opioid receptor into a rapid recycling pathway, to inhibit proteolytic down-regulation of receptors, and to mediate receptor-autonomous sorting of mutant receptors from the wild type allele when co-expressed in the same cells. These observations define a transplantable signal mediating rapid recycling of a heterologous G protein-coupled receptor, and they suggest that rapid recycling of certain membrane proteins does not occur by bulk membrane flow but is instead mediated by a specific endocytic sorting mechanism.