Cross-talk in Neurotransmitter Receptors

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Science  04 Feb 2000:
Vol. 287, Issue 5454, pp. 769
DOI: 10.1126/science.287.5454.769h

Typically, extracellular signals are communicated from a plasma membrane receptor via second messengers to the target effectors. Liu et al. demonstrate that members of distinct neurotransmitter receptor families also may communicate through direct interaction. They report that the type A GABA (γ-aminobutyric acid) receptor, a ligand-gated Cl channel, and the dopamine D5 receptor, a G protein-coupled receptor, inhibit each other's signaling activity through direct contact of their cytoplasmic domains. The interaction between the receptors attenuated the stimulation of adenylyl cyclase triggered by dopamine and diminished chloride currents induced by GABA. Analysis of cultured hippocampal neurons suggest that the complex formation is physiologically relevant: the two receptors co-localize, and a D5 receptor agonist decreased GABAA receptor—mediated current. It remains to be determined whether other co-localized receptors also undergo regulation through such direct protein-protein interaction.—NG

Nature403, 274 (2000).

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