GPCR activation and FRET

A recent mini-review article on G-protein and GPCR activation involving FRET study was nicely described by Vilardaga et al (Mol Endocrinol. 2009 Feb). It is a nice paper giving background on GPCR as well as the principles of FRET and describe the mechanisms of GPCr activation using this technology. The abstract of the paper states that : Many biochemical pathways are driven by G protein-coupled receptors (GPCRs), cell surface proteins that convert the binding of extracellular chemical, sensory, and mechanical stimuli into cellular signals. Their interaction with various ligands triggers receptor activation that typically couples to and activates heterotrimeric G proteins, which in turn control the propagation of secondary messenger molecules (e.g. cAMP) involved in critically important physiological processes (e.g. heart beat). Successful transfer of information from ligand binding events to intracellular signaling cascades involves a dynamic interplay between ligands, receptors, and G proteins. The development of FRET and BRET-based methods has now permitted the kinetic analysis of initial steps involved in GPCR-mediated signaling in live cells, and in systems as diverse as neurotransmitter and hormone signaling. The direct measurement of ligand efficacy at the level of the receptor by FRET is also now possible, and allows intrinsic efficacies of clinical drugs to be linked with the effect of receptor polymorphisms.