突触后密度蛋白95（PSD-95）调节D1多巴胺受体的再敏化，但不调节受体介导的Gs蛋白激活。

Sun Peihua, Wang Jingru, Gu Weihua, Cheng Wei, Jin Guo-zhang, Friedman Eitan, Zheng Jie, Zhen Xuechu

State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Cell Res. 2009 May;19(5):612-24. doi: 10.1038/cr.2009.30.

The present study aims to define the role of postsynaptic density (PSD)-95 in the regulation of dopamine (DA) receptor function. We found that PSD-95 physically associates with either D(1) or D(2) DA receptors in co-transfected HEK-293 cells. Stimulation of DA receptors altered the association between D(1) receptor and PSD-95 in a time-dependent manner. Functional assays indicated that PSD-95 co-expression did not affect D(1) receptor-stimulated cAMP production, Gs-protein activation or receptor desensitization. However, PSD-95 accelerated the recovery of internalized membrane receptors by promoting receptor recycling, thus resulting in enhanced resensitization of internalized D(1) receptors. Our results provide a novel mechanism for regulating DA receptor recycling that may play an important role in postsynaptic DA functional modulation and synaptic neuroplasticity.

本研究旨在确定突触后致密蛋白95（PSD-95）在多巴胺（DA）受体功能调节中的作用。我们发现，在共转染的HEK-293细胞中，PSD-95与D1或D2 DA受体存在物理关联。刺激DA受体会以时间依赖性方式改变D1受体与PSD-95之间的关联。功能分析表明，PSD-95共表达不影响D1受体刺激的cAMP产生、Gs蛋白激活或受体脱敏。然而，PSD-95通过促进受体内吞循环加速内化膜受体的恢复，从而增强内化D1受体的再敏化。我们的结果提供了一种调节DA受体内吞循环的新机制，这可能在突触后DA功能调节和突触神经可塑性中起重要作用。