PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation.
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 D(1) or D(2) DA receptors in co-transfected HEK-293 cells. Stimulation of DA receptors altered the association between D(1) receptor and PSD-95 in a time-dependent manner. Functional assays indicated that PSD-95 co-expression did not affect D(1) 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 D(1) 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.
Sun
Peihua
P
State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Wang
Jingru
J
Gu
Weihua
W
Cheng
Wei
W
Jin
Guo-zhang
GZ
Friedman
Eitan
E
Zheng
Jie
J
Zhen
Xuechu
X
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004298:Dopamine / Q000494:pharmacology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013997:Time Factors
C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D004298:Dopamine