Research ArticleGPCR SIGNALING

Single-molecule diffusion-based estimation of ligand effects on G protein–coupled receptors

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Science Signaling  18 Sep 2018:
Vol. 11, Issue 548, eaao1917
DOI: 10.1126/scisignal.aao1917

Tracking receptor dynamics

Methods to determine the effect of a drug on a given G protein–coupled receptor (GPCR) often rely on monitoring intracellular molecules affected by the signaling pathway of that receptor. However, how can the effects of drugs be determined for GPCRs whose signaling pathways are unclear? Using single-molecule imaging of the diffusion of different classes of known GPCRs in the plasma membrane, Yanagawa et al. showed that the dynamics of GPCR movement could be classified into four groups depending on whether the interacting drug activated or inhibited the receptor. The coupling of GPCRs to G proteins and receptor endocytosis also resulted in defined diffusion characteristics, suggesting that analyzing the diffusion coefficient of a GPCR provides an estimate of the effect that a candidate drug has.

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