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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)612-624
Number of pages13
JournalCell Research
Volume19
Issue number5
DOIs
StatePublished - 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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