title: Approaches to Assess Functional Selectivity in GPCRs: Evaluating G Protein Signaling in an Endogenous Environment.
abstract: Ligand-directed signaling, biased agonism, and functional selectivity are terms that describe the propensity of a ligand to drive signaling toward one GPCR pathway over another. Most of the early examples demonstrated to date examine the divergence between GPCR signaling to G protein coupling and βarrestin2 recruitment. As biased agonists begin to become available based on cell-based screening criteria, a need arises to determine if G protein signaling biases will be maintained in the endogenous setting, wherein receptors are functioning to control relevant biological responses. This report presents our method and offers tips for evaluating G protein signaling in endogenous tissues. Predominately, brain tissues are discussed here; optimization points that can be applied to any tissues are highlighted.
authors.affiliation: Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute, 130 Scripps Way #2A2, Jupiter, FL, 33458, USA, lbohn@scripps.edu.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bohn
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Jo-Hao
authors.initials: JH
authors.lastname: Ho
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins