Interaction of dopamine D1 receptor with N-ethylmaleimide-sensitive factor is important for the membrane localization of the receptor.
The dopamine D1 receptor (D1R) plays important roles in regulating motor coordination, working memory, learning, and reward. In the mammalian brain, D1R is localized predominantly in dendritic spines. However, the molecular mechanisms involved in the transport, sorting, and targeting of D1R to dendritic spines are largely unknown. Here, we characterize the interaction between D1R and N-ethylmaleimide-sensitive factor (NSF) and show that the interaction is mediated by aa 387-401 of the D1R C-terminal tail. Interfering D1R and NSF interaction by coexpressing GFP-D1R aa 387-401 fusion protein reduces D1R membrane localization and inhibits D1R mediated cAMP accumulation. Treatment of hippocampal neurons with Tat-D1R aa 387-401 decreases the synaptic localization of D1R and the cell surface expression of D1R, but not the cell surface expression of alpha7 nicotinic receptor. Our data indicate that the interaction between NSF and D1R is important for the membrane localization of D1R.
Chen
Sheng
S
Department of Neuroscience, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Liu
Fang
F
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D049229:Dendritic Spines / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; D011956:Receptors, Cell Surface; D017447:Receptors, Dopamine D1; D011993:Recombinant Fusion Proteins; D000242:Cyclic AMP; D005982:Glutathione Transferase; D000251:Adenosine Triphosphatases; D052066:N-Ethylmaleimide-Sensitive Proteins