PDZ-mediated interactions retain the epithelial GABA transporter on the basolateral surface of polarized epithelial cells
PDZ-mediated interactions retain the epithelial GABA transporter on the basolateral surface of polarized epithelial cells
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DOI：
10.1093/emboj/18.9.2384
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发表时间：
1999-05-04
期刊：
影响因子：
11.4
通讯作者：
Pietrini, G
中科院分区：
文献类型：
--
作者：
Perego, C;Vanoni, C;Pietrini, G
PDZ 靶基序位于许多受体和离子通道的 C 末端，通过与特定的含有 PDZ 的蛋白质结合来介导蛋白质-蛋白质相互作用。这些相互作用涉及表面蛋白在神经元和上皮细胞的专门膜域上的定位。然而，这种 PDZ 蛋白依赖性极化定位的分子机制仍不清楚。本研究首先证明上皮γ-氨基丁酸（GABA）转运蛋白（BGT-1）含有一个PDZ靶基序，介导与Madin-Darby犬肾（MDCK）细胞中PDZ蛋白LIN-7的相互作用，然后研究了这种相互作用在转运蛋白的基底外侧定位中的作用，发现虽然删除了PDZ靶基序的转运蛋白仍然靶向于基底外侧表面，但它们并没有被保留，而是被保留下来。此外，干扰性 BGT 肽决定了天然转运蛋白的细胞内重新定位。这些数据表明，与 PDZ 蛋白的相互作用通过保留而非靶向机制决定了靶蛋白的极化表面定位。因此，PDZ 蛋白可能充当一种膜蛋白分选机制，通过识别保留信号（PDZ 靶序列）来防止蛋白质内化。
The PDZ target motifs located in the C-terminal end of many receptors and ion channels mediate protein-protein interactions by binding to specific PDZ-containing proteins, These interactions are involved in the localization of surface proteins on specialized membrane domains of neuronal and epithelial cells. However, the molecular mechanism responsible for this PDZ protein-dependent polarized localization is still unclear. This study first demonstrated that the epithelial gamma-aminobutyric acid (GABA) transporter (BGT-1) contains a PDZ target motif that mediates the interaction with the PDZ protein LIN-7 in Madin-Darby canine kidney (MDCK) cells, and then investigated the role of this interaction in the basolateral localization of the transporter, It was found that although the transporters from which the PDZ target motif was deleted were still targeted to the basolateral surface, they were not retained but internalized in an endosomal recycling compartment, Furthermore, an interfering BGT peptide determined the intracellular relocation of the native transporter. These data indicate that interactions with PDZ proteins determine the polarized surface localization of target proteins by means of retention and not targeting mechanisms. PDZ proteins may, therefore, act as a sort of membrane protein sorting machinery which, by recognizing retention signals (the PDZ target sequences), prevents protein internalization.