GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs
GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs
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DOI：
10.1073/pnas.0703368104
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发表时间：
2007-06-05
影响因子：
11.1
通讯作者：
Tocchini-Valentini, Glauco P.
中科院分区：
文献类型：
--
作者：
Marazziti, Daniela;Mandillo, Silvia;Tocchini-Valentini, Glauco P.
孤儿G蛋白偶联受体37（GPR 37）是帕金的底物;它的不溶性聚集体在帕金森病患者的大脑样本中积累。我们在这里报告说，GPR 37与多巴胺转运蛋白（DAT）相互作用，并调节DAT的活动。GPR 37和DAT被发现共定位在小鼠纹状体突触前膜和转染细胞中，它们的相互作用通过共免疫沉淀试验得到证实。Gpr 37无效突变小鼠纹状体膜样品中DAT介导的多巴胺摄取增强，质膜DAT分子数量显著增加。无效突变小鼠也表现出可卡因诱导的运动活动减少和多巴胺受体拮抗剂诱导的僵住症。这些结果揭示了GPR 37，一个假定的肽能G蛋白偶联受体，在调节DAT的功能表达和多巴胺能药物的行为反应的具体作用。
The orphan G protein-coupled receptor 37 (GPR37) is a substrate of parkin; its insoluble aggregates accumulate in brain samples of Parkinson's disease patients. We report here that GPR37 interacts with the dopamine transporter (DAT) and modulates DAT activity. GPR37 and DAT were found colocalized in mouse striatal-presynaptic membranes and in transfected cells and their interaction was confirmed by coimmunoprecipitation assays. Gpr37-null mutant mice showed enhanced DAT-mediated dopamine uptake in striatal membrane samples, with a significant increase in the number of plasma membrane DAT molecules. The null mutant mice also exhibited a decrease in cocaine-induced locomotor activity and in catalepsy induced by dopamine receptor antagonists. These results reveal the specific role of GPR37, a putative peptidergic G protein-coupled receptor, in modulating the functional expression of DAT and the behavioral responses to dopaminergic drugs.