Oligomeric assembly of dopamine D₁ and glutamate NMDA receptors: molecular mechanisms and functional implications

In the striatum, dopamine D₁R (D₁ 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 D₁R forms a heteromeric complex with the NMDAR (NMDA receptor) and that this mechanism is crucial to recruit the D₁R to the postsynaptic density. By using confocal and radioligand-binding assay, we also demonstrated that the interaction with NMDAR abolishes agonist-mediated D₁R sequestration, indicating that oligomerization with NMDAR could represent a novel regulatory mechanism modulating D₁R cellular trafficking and desensitization.