Dopamine D1 receptor – NMDA receptor GluN1 subunit protein-protein interface (D1R-GluN1 PPI) (D1R-GluN1 PPI)

The Dopamine D1 receptor – NMDA receptor GluN1 subunit protein-protein interface is a specialized molecular complex formed by the direct physical coupling of the G protein-coupled Dopamine D1 receptor (D1R) and the ionotropic NMDA receptor subunit 1 (GluN1). This interaction occurs via the carboxyl-terminal tails of both receptors and plays a critical role in modulating glutamatergic neurotransmission and synaptic plasticity in the central nervous system, particularly within the striatum and hippocampus (Lee et al., 2002, Cell). By forming this complex, D1R activation can either enhance or inhibit NMDA receptor-mediated currents, thereby regulating neuronal excitability and long-term potentiation (LTP). Dysregulation of the D1R-GluN1 interface is strongly linked to the pathophysiology of schizophrenia, where it contributes to NMDA receptor hypofunction, and to Parkinson's disease, where it may influence the development of L-DOPA-induced dyskinesia (Pei et al., 2004, Journal of Neuroscience). Therapeutic targeting of this interface using interference peptides, such as Tat-D1-t2, offers a precise method to decouple these signaling pathways without the broad side effects of global receptor agonists or antagonists (Nai et al., 2010, Molecular Brain). This target is of significant interest for developing treatments that restore cognitive function and motor control by fine-tuning the crosstalk between dopaminergic and glutamatergic systems.

Other names

D1-NMDA receptor complexD1R-GluN1 heteromerD1-GluN1 interactionDopamine D1 receptor-ionotropic glutamate receptor NMDA type subunit 1 complex

Modulation of NMDA receptor-mediated signaling through the physical disruption or stabilization of the direct interaction between the C-terminal tails of the Dopamine D1 receptor and the GluN1 subunit (Lee et al., 2002, Cell).