Volume 19, No 5, May 2009

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 19 Issue 5, May 2009: 612-624

ORIGINAL ARTICLES

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

Peihua Sun^1,*, Jingru Wang^1,*, Weihua Gu^1,*, Wei Cheng², Guo-zhang Jin¹, Eitan Friedman³, Jie Zheng² and Xuechu Zhen¹

¹State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

²Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA 95616, USA

³Department of Physiology & Pharmacology, CUNY Medical School at CCNY, New York, NY, USA Correspondence: Xuechu Zhen,(xczhen@mail.shcnc.ac.cn)

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-dependent manner. Functional assays indicated that PSD-95 co-expression did not affect D₁ 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 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.

Cell Research (2009) 19:612-624. doi: 10.1038/cr.2009.30; published online 10 March 2009

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