GPR37与多巴胺转运体结合，以调节多巴胺摄取及对多巴胺能药物的行为反应。
GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs.
作者信息
Marazziti Daniela, Mandillo Silvia, Di Pietro Chiara, Golini Elisabetta, Matteoni Rafaele, Tocchini-Valentini Glauco P
机构信息
Istituto di Biologia Cellulare-Consiglio Nazionale delle Ricerche, Campus A. Buzzati-Traverso, Via E. Ramarini 32, Monterotondo Scalo, I-00015 Rome, Italy.
出版信息
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9846-51. doi: 10.1073/pnas.0703368104. Epub 2007 May 22.
Abstract
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.
摘要
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。
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本文引用的文献
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Dopamine transporter cell surface localization facilitated by a direct interaction with the dopamine D2 receptor.多巴胺转运体在细胞表面的定位通过与多巴胺D2受体的直接相互作用而得以促进。
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D2 receptors regulate dopamine transporter function via an extracellular signal-regulated kinases 1 and 2-dependent and phosphoinositide 3 kinase-independent mechanism.D2受体通过细胞外信号调节激酶1和2依赖性且磷脂酰肌醇3激酶非依赖性机制调节多巴胺转运体功能。
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Trace amine-associated receptor 1 is a modulator of the dopamine transporter.痕量胺相关受体1是多巴胺转运体的调节剂。
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Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation.帕金蛋白缺失时，帕伊受体通过内质网应激和多巴胺毒性诱导黑质多巴胺能神经元死亡，且这种作用会增强。
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Mice lacking the alpha4 nicotinic receptor subunit fail to modulate dopaminergic neuronal arbors and possess impaired dopamine transporter function.缺乏α4烟碱样受体亚基的小鼠无法调节多巴胺能神经元树突，并具有受损的多巴胺转运体功能。
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Environmental enrichment decreases cell surface expression of the dopamine transporter in rat medial prefrontal cortex.环境富集降低大鼠内侧前额叶皮质中多巴胺转运体的细胞表面表达。
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