Regulation of anterograde transport of α2-adrenergic receptors by the N termini at multiple intracellular compartments
Regulation of anterograde transport of α2-adrenergic receptors by the N termini at multiple intracellular compartments
复制标题
DOI：
10.1074/jbc.m605734200
复制
发表时间：
2006-12-15
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;Wu, Guangyu
关于G蛋白偶联受体(GPCRs)出口贩运的内在结构决定因素的研究主要集中在受体的C末端。在本报告中，我们确定了α(2)-肾上腺素能受体(α(2)-ARs)的胞外N末端在内质网(ER)通过高尔基体到细胞表面的顺行运输中的作用。N端截短的α(2B)-AR突变体完全不能靶向细胞表面。单个Met-6残基对于内质网中α(2B)-AR的输出是必不可少的，可能是通过调制内质网中正确的α(2B)-AR折叠。Tyr-Ser基序在所有α(2)-AR亚型的膜近端N端高度保守，是α(2A)-AR和α(2B)-AR退出高尔基体所必需的，因此代表着一个新的基于Tyr的基序在高尔基体水平上调节GPCR转运。这些数据提供了第一个证据，表明GPCRs的N端在沿着分泌途径从不同的细胞内隔间输出的过程中发挥重要作用。
The studies on the intrinsic structural determinants for export trafficking of G protein-coupled receptors (GPCRs) have been mainly focused on the C termini of the receptors. In this report we determined the role of the extracellular N termini of alpha(2)-adrenergic receptors (alpha(2)-ARs) in the anterograde transport from the endoplasmic reticulum ( ER) through the Golgi to the cell surface. The N-terminal-truncated alpha(2B)-AR mutant is completely unable to target to the cell surface. A single Met-6 residue is essential for the export of alpha(2B)-AR from the ER, likely through modulating correct alpha(2B)-AR folding in the ER. The Tyr-Ser motif, highly conserved in the membrane-proximal N termini of all alpha(2)-AR subtypes, is required for the exit of alpha(2A)-AR and alpha(2B)-AR from the Golgi apparatus, thus representing a novel Tyr-based motif modulating GPCR transport at the Golgi level. These data provide the first evidence indicating an essential role of the N termini of GPCRs in the export from distinct intracellular compartments along the secretory pathway.