Exploring the Biology of G Protein–Coupled Receptors from In Vitro to In Vivo

Abstract

In August 2014, an international group of researchers gathered for 5 days at the Lorentz Center in Leiden, The Netherlands, to explore the technical and conceptual issues associated with the analysis of G protein-coupled receptor functions utilizing information from crystal structure models to the use of model organisms. This collection of review articles evolved from the 5-day meeting, with brief presentations and structured discussion periods that were designed to identify key questions remaining in understanding G protein-coupled receptor function and to propose novel strategies by integrating scientific disciplines to guide future research.

In vivo brain GPCR signaling elucidated by phosphoproteomics

“…Functional selectivity, a GPCR signaling paradigm derived from in vitro 8,9 and structural 10 experiments, was used to explain this phenomenon 11,12 . However, KOR functional selectivity in cells transfected with KOR is not directly translatable to cells naturally expressing KOR 13 or into behavioral effects in vivo 14 . Especially the complexity of brain circuitry hinders the in vitro-in vivo correlation through heterogeneity at cellular, pathways, and protein levels 15 .…”

New Technologies for Elucidating Opioid Receptor Function

“…Given that many of these receptors are co-expressed, these new tools may provide a multiplexed method for dissecting receptor interactions, signaling, and circuit level effects in vitro and in vivo . Future studies are warranted to determine how opto-opioid-like receptors function in peripheral circuits, and whether they can be further mutated or enhanced to better mimic endogenous opioid receptor function, as well as to better dissect the role of biased opioid receptor signaling in vivo with spatiotemporal control (28) (68) (69). …”