Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools

Abstract G-protein-coupled receptors (GPCRs) control various downstream signaling pathways, with multiple effectors whose interactions are subject to sophisticated regulation to achieve signaling specificity. Spatiotemporal organization of GPCR signaling is essential for efficient control of multifa...

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Main Authors: Yonghoon Kwon, Sohum Mehta, Jin Zhang
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Experimental and Molecular Medicine
Online Access:https://doi.org/10.1038/s12276-025-01485-2
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author Yonghoon Kwon
Sohum Mehta
Jin Zhang
author_facet Yonghoon Kwon
Sohum Mehta
Jin Zhang
author_sort Yonghoon Kwon
collection DOAJ
description Abstract G-protein-coupled receptors (GPCRs) control various downstream signaling pathways, with multiple effectors whose interactions are subject to sophisticated regulation to achieve signaling specificity. Spatiotemporal organization of GPCR signaling is essential for efficient control of multifaceted signaling pathways. To study how this spatiotemporal signaling is structured and affects cellular functionality, various genetically encoded molecular tools that can detect and perturb the target biochemical activities at a subcellular level have been developed. In this Review, we introduce various types of fluorescent protein-based biosensors and molecular tools that allow us to directly elucidate the spatiotemporal mechanisms of GPCR signaling regulation at a subcellular level. Finally, we highlight several applications of these molecular tools to study the spatiotemporal organization of GPCR in living cells to obtain a comprehensive understanding of the signaling architecture.
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spelling doaj-art-0e2fa86d41f44c19944e2ac0d06e7a612025-08-20T03:42:34ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-07-015771432144210.1038/s12276-025-01485-2Probing spatiotemporally organized GPCR signaling using genetically encoded molecular toolsYonghoon Kwon0Sohum Mehta1Jin Zhang2Department of Pharmacology, University of California San DiegoDepartment of Pharmacology, University of California San DiegoDepartment of Pharmacology, University of California San DiegoAbstract G-protein-coupled receptors (GPCRs) control various downstream signaling pathways, with multiple effectors whose interactions are subject to sophisticated regulation to achieve signaling specificity. Spatiotemporal organization of GPCR signaling is essential for efficient control of multifaceted signaling pathways. To study how this spatiotemporal signaling is structured and affects cellular functionality, various genetically encoded molecular tools that can detect and perturb the target biochemical activities at a subcellular level have been developed. In this Review, we introduce various types of fluorescent protein-based biosensors and molecular tools that allow us to directly elucidate the spatiotemporal mechanisms of GPCR signaling regulation at a subcellular level. Finally, we highlight several applications of these molecular tools to study the spatiotemporal organization of GPCR in living cells to obtain a comprehensive understanding of the signaling architecture.https://doi.org/10.1038/s12276-025-01485-2
spellingShingle Yonghoon Kwon
Sohum Mehta
Jin Zhang
Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools
Experimental and Molecular Medicine
title Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools
title_full Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools
title_fullStr Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools
title_full_unstemmed Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools
title_short Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools
title_sort probing spatiotemporally organized gpcr signaling using genetically encoded molecular tools
url https://doi.org/10.1038/s12276-025-01485-2
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