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Abundance and stability of complexes containing inactive G protein-coupled receptors and G proteins.| Authors: | Kou Qin, Pooja R Sethi, Nevin A Lambert | | Language: | ENG. | | Date: | 24-4-2008 | | Journal: | The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(1530-6860)
| | Release: | FASEB J. 23 Apr 2008 | |
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Abstract:
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G protein-coupled receptors (GPCRs) interact directly with heterotrimeric G proteins to transduce physiological signals. Early studies of this interaction concluded that GPCRs (R) and G proteins (G) collide with each other randomly after receptor activation and that R-G complexes are transient. More recent studies have suggested that inactive R and G are preassembled (precoupled) as stable R-G complexes. Here we examine the stability of complexes formed between cyan fluorescent protein-labeled alpha2A-adrenoreceptors (C-alpha2ARs) and G proteins in cells using fluorescence recovery after photobleaching (FRAP). Labeled G proteins diffused in the plasma membrane with equal mobility in the absence and presence of immobile C-alpha2ARs. Immobile C-alpha2ARs activated labeled G proteins, demonstrating functional coupling without stable physical association. In contrast, a stable R-G interaction was detected when G proteins were deprived of nucleotides and C-alpha2ARs were active, as predicted by the ternary complex model. Overexpression of regulator of G protein signaling 4 (RGS4) accelerated the onset of effector activation but did not detectably alter the interaction between C-alpha2ARs and G proteins. We conclude that at most a small fraction of C-alpha2ARs and G proteins exist as R-G complexes at any moment.-Qin, K., Sethi, P. R., Lambert, N. I. Abundance and stability of complexes containing inactive G protein-coupled receptors and G proteins.
| | Copyright: | The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Graduate Program in Neuroscience and Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia, USA. | | Full text: | | | |
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