Marazziti Daniela, Mandillo Silvia, Di Pietro Chiara, Golini Elisabetta, Matteoni Rafaele, Tocchini-Valentini Glauco P
Istituto di Biologia Cellulare-Consiglio Nazionale delle Ricerche, Campus A. Buzzati-Traverso, Via E. Ramarini 32, Monterotondo Scalo, I-00015 Rome, Italy.
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9846-51. doi: 10.1073/pnas.0703368104. Epub 2007 May 22.
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.
孤儿G蛋白偶联受体37（GPR37）是帕金的底物；其不溶性聚集体在帕金森病患者的脑样本中积累。我们在此报告，GPR37与多巴胺转运体（DAT）相互作用并调节DAT活性。GPR37和DAT在小鼠纹状体突触前膜和转染细胞中共定位，并且通过免疫共沉淀试验证实了它们的相互作用。Gpr37基因敲除突变小鼠在纹状体膜样本中显示出增强的DAT介导的多巴胺摄取，质膜DAT分子数量显著增加。基因敲除突变小鼠还表现出可卡因诱导的运动活性降低以及多巴胺受体拮抗剂诱导的僵住症减少。这些结果揭示了一种假定的肽能G蛋白偶联受体GPR37在调节DAT的功能表达以及对多巴胺能药物的行为反应中的特定作用。
