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Chunk #9 — RGS proteins: a member of the macromolecular signaling club

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Addictive drugs modulate GIRK-channel signaling by regulating RGS proteins.
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for baclofen activation [1][29] and DA neurons uniquely express GIRK2/GIRK3 channels. We observed a similar decrease in EC50 in GIRK3 knockout mice as well as in RGS2/GIRK3 double-knockout mice [2]. These findings suggest that RGS2 specifically modulates the coupling to channels containing GIRK3. Indeed, a close association between GIRK3 and RGS2 is detected using FRET spectroscopic measurements [2]. Thus, specific protein-protein interactions among RGS proteins, G-proteins, GIRK channels and GABAB receptors may be involved in establishing macromolecular signaling complexes that fine-tune the coupling efficiency of GPCR signaling.