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EMERGING TECHNOLOGY

Engineered GPCRs as Tools to Modulate Signal Transduction

Ying Pei, Sarah C. Rogan, Feng Yan and Bryan L. Roth

Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, bryan_roth{at}med.unc.edu

Different families of G-protein-coupled receptors (GPCRs) have been engineered to provide exclusive control over the activation of these receptors and thus to understand better the consequences of their signaling in vitro and in vivo. These engineered receptors, named RASSLs (receptors activated solely by synthetic ligands) and DREADDs (designer receptors exclusively activated by designer drugs), are insensitive to their endogenous ligands but can be activated by synthetic drug-like compounds. Currently, the existing RASSLs and DREADDs cover the G_i, G_q, and G_s signaling pathways. These modified GPCRs can be utilized as ideal tools to study GPCR functions selectively in specific cellular populations.