Editors' ChoiceNeurobiology

Regulation by Direct Contact

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Science's STKE  25 Jan 2000:
Vol. 2000, Issue 16, pp. tw5
DOI: 10.1126/stke.2000.16.tw5

Typically extracellular signals are transduced from a plasma membrane receptor through second messengers to the target effectors. Liu et al. demonstrate that members of distinct receptor families may also communicate through direct interaction. They report that the GABAA receptor, a ligand-gated Cl- channel, and the dopamine D5 receptor, a G protein-coupled receptor, inhibit each other's activity through direct contact. In coprecipitation experiments, GABAA receptor subunits from hippocampal extracts could be identified after immunoprecipitation with D5 receptor antibodies. The formation of such complexes in HEK293 cells expressing both proteins was agonist dependent. The interaction between the receptors decreased both cAMP formation stimulated by the D5 receptor and currents mediated by the GABAA receptor. The interaction was specific to the D5 receptor and did not occur with D1 receptors. Data from cultured hippocampal neurons suggest that the complex formation is physiologically relevant: The two receptors colocalize, and under conditions in which the protein kinase A and protein kinase C pathways were blocked, a D5 receptor agonist decreased GABAA-receptor-mediated currents. It remains to be determined whether other colocalized receptors also undergo regulation through such direct protein-protein interaction.

Liu, F., Wan, Q., Pristupa, Z.B., Yu, X.-M., Wang, Y.T., and Niznik, H.B. (2000) Direct protein-protein coupling enables cross-talk between dopamine D5 and γ-aminobutyric acid A receptors. Nature 403: 274-280. [Online Journal]

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