Investigating G-protein coupled receptor signalling with light-emitting biosensors

Alexander Demby; Manuela Zaccolo

doi:10.3389/fphys.2023.1310197

Investigating G-protein coupled receptor signalling with light-emitting biosensors

Front Physiol. 2024 Jan 8:14:1310197. doi: 10.3389/fphys.2023.1310197. eCollection 2023.

Authors

Alexander Demby¹, Manuela Zaccolo¹

Affiliation

¹ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.

Abstract

G protein-coupled receptors (GPCRs) are the most frequent target of currently approved drugs and play a central role in both physiological and pathophysiological processes. Beyond the canonical understanding of GPCR signal transduction, the importance of receptor conformation, beta-arrestin (β-arr) biased signalling, and signalling from intracellular locations other than the plasma membrane is becoming more apparent, along with the tight spatiotemporal compartmentalisation of downstream signals. Fluorescent and bioluminescent biosensors have played a pivotal role in elucidating GPCR signalling events in live cells. To understand the mechanisms of action of the GPCR-targeted drugs currently available, and to develop new and better GPCR-targeted therapeutics, understanding these novel aspects of GPCR signalling is critical. In this review, we present some of the tools available to interrogate each of these features of GPCR signalling, we illustrate some of the key findings which have been made possible by these tools and we discuss their limitations and possible developments.

Keywords: BRET; FRET; G protein; GPCR; bioluminescence; fluorescent biosensor; signalling.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. AD is funded by a studentship from Sir Michael Moritz and Harriet Heyman, founders of the Crankstart Foundation MZ is funded by the British Heart Foundation (BHF; PG/15/5/31110 and RG/17/6/32944) and the BHF Centre of Research Excellence, Oxford (RE/13/1/30181, RE/18/3/34214, and RE/18/3/34214) and the Oxford NIHR Biomedical Research Centre. Figures were created using BioRender.