Bioluminescent tools for the analysis of G-protein-coupled receptor and arrestin interactions

Abstract

G protein-coupled receptors (GPCRs) play crucial roles in numerous physiological and disorder-related processes. Because GPCRs are regarded as a target of many therapeutics, various methods for their analyses have been developed and applied for high-throughput screening of large chemical libraries. As a complement to the traditional analysis of second messengers and gene expression, direct monitoring of GPCR behavior is now indispensable for the identification and accurate analysis of novel chemicals. This review presents new protein-based bioluminescent probes for monitoring GPCR interaction with β-arrestin, a cytoplasmic protein that binds to GPCRs. The principle is based mainly on bioluminescence resonance energy transfer (BRET) and protein fragment complementation (PCA) techniques, which can advance GPCR drug discovery technologies.