A multi-dimensional view of context-dependent G protein-coupled receptor function

Abstract

G protein-coupled receptor (GPCR) family members can sense an extraordinary variety of biomolecules to activate intracellular signalling cascades that modulate key aspects of cell physiology. Apart from their crucial role in maintaining cell homeostasis, these critical sensory and modulatory properties have made GPCRs the most successful drug target class to date. However, establishing direct links between receptor activation of specific intracellular partners and individual physiological outcomes is still an ongoing challenge. By studying this receptor signalling complexity at increasing resolution through the development of novel biosensors and high-throughput techniques, a growing number of studies are revealing how receptor function can be diversified in a spatial, temporal or cell-specific manner. This mini-review will introduce recent examples of this context-dependent receptor signalling and discuss how it can impact our understanding of receptor function in health and disease, and contribute to the search of more selective, efficacious and safer GPCR drug candidates.