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

Niznik, Hyman B ; Liu, Fang ; Wan, Qi ; Pristupa, Zdenek B ; Yu, Xian-Min ; Wang, Yu Tian

Nature (London), 2000-01, Vol.403 (6767), p.274-280 [Periódico revisado por pares]

London: Nature Publishing

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Título:
Direct protein-protein coupling enables cross-talk between dopamine D5 and γ-aminobutyric acid A receptors
Autor: Niznik, Hyman B ; Liu, Fang ; Wan, Qi ; Pristupa, Zdenek B ; Yu, Xian-Min ; Wang, Yu Tian
Assuntos: Amino Acid Motifs ; Animals ; Benzazepines - pharmacology ; Biological and medical sciences ; Cell Line ; Cells, Cultured ; Central nervous system ; Central neurotransmission. Neuromudulation. Pathways and receptors ; Cyclic AMP - metabolism ; Dopamine - metabolism ; Dopamine - pharmacology ; Dopamine Agonists - pharmacology ; Enzymes ; Fundamental and applied biological sciences. Psychology ; GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; gamma-Aminobutyric Acid - metabolism ; gamma-Aminobutyric Acid - pharmacology ; Hippocampus - cytology ; Hippocampus - metabolism ; Humans ; Ligands ; Molecular biology ; Neurology ; Neurons ; Neurons - metabolism ; Proteins ; Rats ; Receptor Cross-Talk ; Receptors, Dopamine D1 - agonists ; Receptors, Dopamine D1 - chemistry ; Receptors, Dopamine D1 - metabolism ; Receptors, Dopamine D5 ; Receptors, GABA-A - chemistry ; Receptors, GABA-A - metabolism ; Recombinant Fusion Proteins - metabolism ; Synaptic Transmission - drug effects ; Transfection ; Vertebrates: nervous system and sense organs
É parte de: Nature (London), 2000-01, Vol.403 (6767), p.274-280
Notas: ObjectType-Article-2
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Descrição: 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.
Editor: London: Nature Publishing
Idioma: Inglês

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

Niznik, Hyman B ; Liu, Fang ; Wan, Qi ; Pristupa, Zdenek B ; Yu, Xian-Min ; Wang, Yu Tian

London: Nature Publishing

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