Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
J Biol Chem. 2011 Jun 10;286(23):20525-35. doi: 10.1074/jbc.M111.222034. Epub 2011 Apr 20.
The molecular mechanisms underlying the endoplasmic reticulum (ER) export and cell surface transport of nascent G protein-coupled receptors (GPCRs) have just begun to be revealed and previous studies have shown that hydrophobic motifs in the putative amphipathic 8(th) α-helical region within the membrane-proximal C termini play an important role. In this study, we demonstrate that di-acidic motifs in the membrane-distal, nonstructural C-terminal portions are required for the exit from the ER and transport to the plasma membrane of angiotensin II receptors, but not adrenergic receptors. More interestingly, distinct di-acidic motifs dictate optimal export trafficking of different angiotensin II receptors and export ability of each acidic residue in the di-acidic motifs cannot be fully substituted by other acidic residue. Moreover, the function of the di-acidic motifs is likely mediated through facilitating the recruitment of the receptors onto the ER-derived COPII transport vesicles. Therefore, the di-acidic motifs located in the membrane-distal C termini may represent the first linear motifs which recruit selective GPCRs onto the COPII vesicles to control their export from the ER.
内质网（ER）出口和新生 G 蛋白偶联受体（GPCR）细胞表面转运的分子机制刚刚开始被揭示，先前的研究表明，跨膜近侧 C 末端假定的两亲性 8（th）α螺旋区中的疏水区段发挥着重要作用。在这项研究中，我们证明了膜远端非结构 C 末端的双酸性基序对于血管紧张素 II 受体从 ER 中逸出并转运到质膜是必需的，但对于肾上腺素能受体则不是必需的。更有趣的是，不同的双酸性基序决定了不同血管紧张素 II 受体的最佳出口运输，并且双酸性基序中的每个酸性残基的出口能力不能被其他酸性残基完全取代。此外，双酸性基序的功能可能通过促进受体募集到 ER 衍生的 COPII 运输小泡来介导。因此，位于膜远端 C 末端的双酸性基序可能代表第一个线性基序，它将选择性 GPCR 募集到 COPII 小泡上，以控制它们从 ER 中的输出。
