Spatiotemporal GPCR signaling illuminated by genetically encoded fluorescent biosensors

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Item Type:	Article
Title:	Spatiotemporal GPCR signaling illuminated by genetically encoded fluorescent biosensors
Creators Name:	Kayser, C., Melkes, B., Derieux, C. and Bock, A.
Abstract:	G protein-coupled receptors (GPCRs) are ligand-activated cell membrane proteins and represent the most important class of drug targets. GPCRs adopt several active conformations that stimulate different intracellular G proteins (and other transducers) and thereby modulate second messenger levels, eventually resulting in receptor-specific cell responses. It is increasingly accepted that not only the type of active signaling protein but also the duration of its stimulation and the subcellular location from where receptors signal distinctly contribute to the overall cell response. However, the molecular principles governing such spatiotemporal GPCR signaling and their role in disease are incompletely understood. Genetically encoded, fluorescent biosensors-in particular for the GPCR/cAMP signaling axis-have been pivotal to the discovery and molecular understanding of novel concepts in spatiotemporal GPCR signaling. These include GPCR priming, location bias, and receptor-associated independent cAMP nanodomains. Here, we review such technologies that we believe will illuminate the spatiotemporal organization of other GPCR signaling pathways that define the complex signaling architecture of the cell.
Keywords:	BRET, Cell Signaling, Compartmentation, FRET, Fluorescent Biosensors, G Protein-Coupled Receptors, Nanobodies, Spatiotemporal Signaling, cAMP Nanodomains, ebBRET
Source:	Current Opinion in Pharmacology
ISSN:	1471-4973
Publisher:	Elsevier
Volume:	71
Page Range:	102384
Date:	August 2023
Official Publication:	https://doi.org/10.1016/j.coph.2023.102384
PubMed:	View item in PubMed

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