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.