Modern Methods to Explore GPCR Signalling in Live Cells

Tripp, Emma; O’Brien, Shannon; Calebiro, Davide

doi:10.22541/au.164560899.93337004/v1

Cited by 1 publication

(1 citation statement)

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“…The biggest limitation to explore GPCR intracellular signaling is represented by the fact that cells need to be lysed and this procedure clearly directly affects the temporal and spatial resolution of the biochemical events of these phenomena. A major breakthrough in the field was achieved with the development of fluorescent and bioluminescent resonance energy transfer (FRET/BRET) sensors [ 142 ]. These RET sensors allow monitoring of GPCR signaling in real time without altering the cell homeostasis.…”

Section: Distinctive Signals Generated By Gpcrs In Intracellular Comp...mentioning

confidence: 99%

GPCRs in Intracellular Compartments: New Targets for Drug Discovery

et al. 2022

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The architecture of eukaryotic cells is defined by extensive membrane-delimited compartments, which entails separate metabolic processes that would otherwise interfere with each other, leading to functional differences between cells. G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors, and their signal transduction is traditionally viewed as a chain of events initiated from the plasma membrane. Furthermore, their intracellular trafficking, internalization, and recycling were considered only to regulate receptor desensitization and cell surface expression. On the contrary, accumulating data strongly suggest that GPCRs also signal from intracellular compartments. GPCRs localize in the membranes of endosomes, nucleus, Golgi and endoplasmic reticulum apparatuses, mitochondria, and cell division compartments. Importantly, from these sites they have shown to orchestrate multiple signals that regulate different cell pathways. In this review, we summarize the current knowledge of this fascinating phenomenon, explaining how GPCRs reach the intracellular sites, are stimulated by the endogenous ligands, and their potential physiological/pathophysiological roles. Finally, we illustrate several mechanisms involved in the modulation of the compartmentalized GPCR signaling by drugs and endogenous ligands. Understanding how GPCR signaling compartmentalization is regulated will provide a unique opportunity to develop novel pharmaceutical approaches to target GPCRs and potentially lead the way towards new therapeutic approaches.

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Section: Distinctive Signals Generated By Gpcrs In Intracellular Comp...mentioning

confidence: 99%