Oligomeric assembly of dopamine D1 and glutamate NMDA receptors: molecular mechanisms and functional implications.
In the striatum, dopamine D(1)R (D(1) receptor) activation potentiates NMDA (N-methyl-D-aspartate) transmission and is required for NMDA-mediated long-term potentiation at corticostriatal synapses. By using a combination of co-immunoprecipitation, pull-out with glutathione S-transferase-fusion proteins and bioluminescence resonance energy transfer, we have reported that the D(1)R forms a heteromeric complex with the NMDAR (NMDA receptor) and that this mechanism is crucial to recruit the D(1)R to the postsynaptic density. By using confocal and radioligand-binding assay, we also demonstrated that the interaction with NMDAR abolishes agonist-mediated D(1)R sequestration, indicating that oligomerization with NMDAR could represent a novel regulatory mechanism modulating D(1)R cellular trafficking and desensitization.
Fiorentini
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Division of Pharmacology, Department of Biomedical Sciences and Biotechnology and Centre of Excellence on Diagnostic and Therapeutic Innovation, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Missale
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D000818:Animals; D003342:Corpus Striatum / Q000502:physiology; D046911:Macromolecular Substances; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000737:chemistry / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D046911:Macromolecular Substances; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate