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

Peihua Sun; Jingru Wang; Weihua Gu; Wei Cheng; Guo Zhang Jin; Eitan Friedman; Jie Zheng; Xuechu Zhen

doi:10.1038/cr.2009.30

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

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

Physiology and Membrane Biology

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	612-624
Number of pages	13
Journal	Cell Research
Volume	19
Issue number	5
DOIs	https://doi.org/10.1038/cr.2009.30
State	Published - May 2009

Keywords

Desensitization
Dopamine receptor
Gs-protein activation
PSD-95
Recycling
Resensitization

ASJC Scopus subject areas

Cell Biology
Molecular Biology

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10.1038/cr.2009.30

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

abstract = "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.",

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AU - Friedman, Eitan

AU - Zheng, Jie

AU - Zhen, Xuechu

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