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

20 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

Access to Document

10.1038/cr.2009.30

Fingerprint Dive into the research topics of 'PSD-95 regulates D1 dopamine receptor resensitization,but not receptor-mediated Gs-protein activation'. Together they form a unique fingerprint.

Cite this

@article{10ec693ea11d4a4cb7c4c9d2f9d7804a,

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.",

keywords = "Desensitization, Dopamine receptor, Gs-protein activation, PSD-95, Recycling, Resensitization",

author = "Peihua Sun and Jingru Wang and Weihua Gu and Wei Cheng and Jin, {Guo Zhang} and Eitan Friedman and Jie Zheng and Xuechu Zhen",

year = "2009",

month = may,

doi = "10.1038/cr.2009.30",

language = "English (US)",

volume = "19",

pages = "612--624",

journal = "Cell Research",

issn = "1001-0602",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - PSD-95 regulates D1 dopamine receptor resensitization,but not receptor-mediated Gs-protein activation

AU - Sun, Peihua

AU - Wang, Jingru

AU - Gu, Weihua

AU - Cheng, Wei

AU - Jin, Guo Zhang

AU - Friedman, Eitan

AU - Zheng, Jie

AU - Zhen, Xuechu

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

KW - Desensitization

KW - Dopamine receptor

KW - Gs-protein activation

KW - PSD-95

KW - Recycling

KW - Resensitization

UR - http://www.scopus.com/inward/record.url?scp=67649105509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649105509&partnerID=8YFLogxK

U2 - 10.1038/cr.2009.30

DO - 10.1038/cr.2009.30

M3 - Article

C2 - 19274064

AN - SCOPUS:67649105509

VL - 19

SP - 612

EP - 624

JO - Cell Research

JF - Cell Research

SN - 1001-0602

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this