Engineering GPCR signaling pathways with RASSLs

Department of Medicine, University of California, San Francisco, San Francisco, California, United States
Nature Methods (Impact Factor: 32.07). 09/2008; 5(8):673-8. DOI: 10.1038/nmeth.1232
Source: PubMed


We are creating families of designer G protein-coupled receptors (GPCRs) to allow for precise spatiotemporal control of GPCR signaling in vivo. These engineered GPCRs, called receptors activated solely by synthetic ligands (RASSLs), are unresponsive to endogenous ligands but can be activated by nanomolar concentrations of pharmacologically inert, drug-like small molecules. Currently, RASSLs exist for the three major GPCR signaling pathways (G(s), G(i) and G(q)). We review these advances here to facilitate the use of these powerful and diverse tools.

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    • "Since GPCRs signal through a limited number of canonical pathways including Gs and Gi that ultimately regulate intracellular cAMP levels, we developed a method of inducing regulated Gs signaling in cells by engineered receptors such as RASSLs (receptors activated solely by synthetic ligands). RASSLs are powerful tools for studying GPCR signaling as they no longer respond to endogenous hormones but can be activated by synthetic small-molecule ligands [24]. In addition, RASSLs are small genes easily expressed in constructs and transgenes allowing precise spatial and temporal regulation. "
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