PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation  

作　　者：Peihua Sun Jmgru Wang Welhua Gu Wei Cheng Guo-zhang Jin Eitan Friedman Jie Zheng Xuechu Zhen 

机构地区：[1]State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2]Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA 95616, USA [3]Department of Physiology & Pharmacology, CUNY Medical School at CCNY,, New York, NY, USA

出　　处：《Cell Research》2009年第5期612-624,共13页细胞研究（英文版）

基　　金：Acknowledgments We thank Dr Morgan Sheng （Harvard University, USA） for providing the cDNA construct for PSD-95. This study was sup- ported by the Natural Science Foundation of China （30770662, 30825042）; Hi-Tech Research and Development Program of China （2007AA02Z163）, National Basic Research Program （2009CB2200） to XZ, and funding from the National Institutes of Health （REY016754A） and the American Heart Association （0665201Y） to JZ. Part of this work was conducted in a facility constructed with support from Research Facilities Improvement Program Grant C06-RR-12088-01 from the National Center for Research Resources.

摘　　要：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 D1 or D2 DA receptors in co-transfected HEK-293 cells. Stimulation of DA receptors altered the association between D1 receptor and PSD-95 in a time-depen- dent manner. Functional assays indicated that PSD-95 co-expression did not affect DI receptor-stimulated cAMP pro- duction, 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 D1 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.

关 键 词：PSD-95 dopamine receptor Gs-protein activation DESENSITIZATION recycling RESENSITIZATION 

分 类 号：Q426[生物学—神经生物学] S852.653[生物学—生理学]