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 | |
| State | Published - May 2009 |
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Keywords
- Desensitization
- Dopamine receptor
- Gs-protein activation
- PSD-95
- Recycling
- Resensitization
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
PSD-95 regulates D1 dopamine receptor resensitization,but not receptor-mediated Gs-protein activation. / Sun, Peihua; Wang, Jingru; Gu, Weihua; Cheng, Wei; Jin, Guo Zhang; Friedman, Eitan; Zheng, Jie; Zhen, Xuechu.
In: Cell Research, Vol. 19, No. 5, 05.2009, p. 612-624.Research output: Contribution to journal › Article
}
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 -