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Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors.

GABA(A) (gamma-aminobutyric-acid A) and dopamine D1 and D5 receptors represent two structurally and functionally divergent families of neurotransmitter receptors. The former comprises a class of multi-subunit ligand-gated channels mediating fast interneuronal synaptic transmission, whereas the latter belongs to the seven-transmembrane-domain single-polypeptide receptor superfamily that exerts its biological effects, including the modulation of GABA(A) receptor function, through the activation of second-messenger signalling cascades by G proteins. Here we show that GABA(A)-ligand-gated channels complex selectively with D5 receptors through the direct binding of the D5 carboxy-terminal domain with the second intracellular loop of the GABA(A) gamma2(short) receptor subunit. This physical association enables mutually inhibitory functional interactions between these receptor systems. The data highlight a previously unknown signal transduction mechanism whereby subtype-selective G-protein-coupled receptors dynamically regulate synaptic strength independently of classically defined second-messenger systems, and provide a heuristic framework in which to view these receptor systems in the maintenance of psychomotor disease states.

Pubmed ID: 10659839


  • Liu F
  • Wan Q
  • Pristupa ZB
  • Yu XM
  • Wang YT
  • Niznik HB



Publication Data

January 20, 2000

Associated Grants


Mesh Terms

  • Amino Acid Motifs
  • Animals
  • Benzazepines
  • Cell Line
  • Cells, Cultured
  • Cyclic AMP
  • Dopamine
  • Dopamine Agonists
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Hippocampus
  • Humans
  • Ligands
  • Neurons
  • Rats
  • Receptor Cross-Talk
  • Receptors, Dopamine D1
  • Receptors, Dopamine D5
  • Receptors, GABA-A
  • Recombinant Fusion Proteins
  • Synaptic Transmission
  • Transfection
  • gamma-Aminobutyric Acid