Research ArticleBiophysics

Coupling Mechanism of a GPCR and a Heterotrimeric G Protein During Chemoattractant Gradient Sensing in Dictyostelium

Science Signaling  28 Sep 2010:
Vol. 3, Issue 141, pp. ra71
DOI: 10.1126/scisignal.2000980

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Ligand-Induced Coupling

A long-standing question regarding the activation of heterotrimeric G proteins by G protein–coupled receptors (GPCRs) is whether the association between the GPCR and the G protein is stimulated by the binding of ligand to the receptor, or whether the receptor and G protein are precoupled. Xu et al. addressed this question by measuring the mobilities of fluorescent fusion proteins of cyclic adenosine monophosphate (cAMP) receptor 1 (cAR1), a GPCR for the chemoattractant cAMP, and the Gβ subunit in live Dictyostelium cells. The receptor and G protein moved independently in the plasma membrane and at different speeds. Whereas exposure of cells to cAMP had no effect on the mobility of cAR1, the mobility of a fraction of the faster-moving G proteins was reduced. Together with computer simulations of the effects of various proposed receptor–G protein coupling mechanisms on downstream signaling, these data suggest that the interaction between cAR1 and its G protein does not occur until the receptor is bound to ligand, and provide a means for investigating the G protein–coupling mechanisms of other GPCRs.