Kwon Yonghoon, Mehta Sohum, Zhang Jin
Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Department of Life Sciences, Gwangju Institute of Science and Technology, Gwanju, Republic of Korea.
Exp Mol Med. 2025 Jul 1. 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.
G蛋白偶联受体（GPCRs）控制着各种下游信号通路，有多个效应器，其相互作用受到复杂调控以实现信号特异性。GPCR信号的时空组织对于有效控制多方面的信号通路至关重要。为了研究这种时空信号是如何构建以及如何影响细胞功能的，人们开发了各种可在亚细胞水平检测和干扰目标生化活性的基因编码分子工具。在本综述中，我们介绍了各种基于荧光蛋白的生物传感器和分子工具，这些工具使我们能够在亚细胞水平直接阐明GPCR信号调控的时空机制。最后，我们重点介绍了这些分子工具在研究活细胞中GPCR的时空组织方面的几个应用，以便全面了解信号结构。
