Probing spatiotemporally organized GPCR signaling using genetically encoded molecular tools

• Published in: Experimental & molecular medicine Vol. 57; no. 7; pp. 1432 - 1442
• Main Authors: Kwon, Yonghoon, Mehta, Sohum, Zhang, Jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2025; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13/95; 14; 14/33; 14/34; 14/35; 14/63; 631/1647/1888/2249; 631/1647/245/2225; 631/80/86/2363; 9/10; 96; Adrenergic receptors; Animals; Artificial intelligence; Biomedical and Life Sciences; Biomedicine; Biosensing Techniques - methods; Biosensors; Design; Endosomes; Energy transfer; G protein-coupled receptors; Golgi apparatus; Humans; Kinases; Ligands; Localization; Medical Biochemistry; Microscopy; Molecular Medicine; Organelles; Proteins; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Review; Review Article; Sensors; Signal Transduction; Stem Cells; Visualization; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-025-01485-2

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. Fluorescent tools illuminate subcellular GPCR signaling dynamics G-protein-coupled receptors (GPCRs) are crucial for many body functions, such as sensing light and taste. Researchers focus on understanding GPCR signaling in different cell parts using special tools called biosensors. Biosensors are molecular tools that detect specific biological activities and convert them into visible readouts. The researchers used fluorescent biosensors to track GPCR signaling in real time within living cells. These biosensors help to visualize where and how GPCRs signal from different subcellular organelles, such as endosomes or the Golgi apparatus. This Review discusses recent findings that GPCRs can signal from various subcellular locations, affecting different cellular responses. This research advances our understanding of GPCR signaling by showing that it is more complex and location specific than previously thought. In the future, these insights could lead to new treatments targeting specific GPCR pathways involved in diseases. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.