Clarification of molecular basis of transporter diseases by the comprehensive detection of protein-rotein interactions.

转运蛋白疾病是由多种膜转运蛋白和通道蛋白紊乱引起的。我们利用日本犬红细胞中谷氨酸转运体GLAST的遗传缺陷作为转运体疾病的模型，分析了改变转运体细胞内运输的综合蛋白质-蛋白质相互作用。PDZ结构域蛋白NHERF1和NHERF2分别与内质网和后高尔基区室中的GLAST蛋白相互作用。由于这些蛋白的共表达改变了GLAST的细胞表面表达水平，因此我们认为PDZ结构域蛋白与GLAST的相互作用与GLAST在细胞内运输的紊乱有关。

Transporter diseases are caused by disorders of various membrane transporter and channel proteins. We analyzed the comprehensive protein-protein interactions that alter intracellular traffic of transporters by utilizing the hereditary defects of glutamate transporter GLAST in Japanese dog red cells as a model of the transporter disease. The PDZ domain proteins NHERF1 and NHERF2 interacted with the GLAST proteins in the endoplasmic reticulum and the post-Golgi compartments during the traffic to the plasma membrane, respectively. Since coexpression of these proteins altered the cell surface expression level of GLAST, it is suggested that the interaction of PDZ domain proteins with GLAST is associated with the disorder of intracellular trafficking of GLAST.