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-t...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-depen- dent manner. Functional assays indicated that PSD-95 co-expression did not affect DI receptor-stimulated cAMP pro- duction, 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.展开更多
基金Acknowledgments We thank Dr Morgan Sheng （Harvard University, USA） for providing the cDNA construct for PSD-95. This study was sup- ported by the Natural Science Foundation of China （30770662, 30825042） Hi-Tech Research and Development Program of China （2007AA02Z163）, National Basic Research Program （2009CB2200） to XZ, and funding from the National Institutes of Health （REY016754A） and the American Heart Association （0665201Y） to JZ. Part of this work was conducted in a facility constructed with support from Research Facilities Improvement Program Grant C06-RR-12088-01 from the National Center for Research Resources.
文摘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-depen- dent manner. Functional assays indicated that PSD-95 co-expression did not affect DI receptor-stimulated cAMP pro- duction, 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.
