McNeill Samantha M, Zhao Peishen
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
ARC Centre for Cryo-Electron Microscopy of Membrane Proteins (CCeMMP), Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Br J Pharmacol. 2024 Jul;181(14):2319-2337. doi: 10.1111/bph.16076. Epub 2023 Apr 19.
G protein-coupled receptors (GPCRs) are the most prominent receptors on the surface of the cell and play a central role in the regulation of cardiac and metabolic functions. GPCRs transmit extracellular stimuli to the interior of the cells by activating one or more heterotrimeric G proteins. The duration and intensity of G protein-mediated signalling are tightly controlled by a large array of intracellular mediators, including the regulator of G protein signalling (RGS) proteins. RGS proteins selectively promote the GTPase activity of a subset of Gα subunits, thus serving as negative regulators in a pathway-dependent manner. In the current review, we summarise the involvement of RGS proteins in cardiometabolic function with a focus on their tissue distribution, mechanisms of action and dysregulation under various disease conditions. We also discuss the potential therapeutic applications for targeting RGS proteins in treating cardiometabolic conditions and current progress in developing RGS modulators. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein-Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc.
G蛋白偶联受体（GPCRs）是细胞表面最主要的受体，在心脏和代谢功能的调节中发挥核心作用。GPCRs通过激活一种或多种异源三聚体G蛋白将细胞外刺激传递到细胞内部。G蛋白介导的信号传导的持续时间和强度受到大量细胞内介质的严格控制，包括G蛋白信号调节剂（RGS）蛋白。RGS蛋白选择性地促进一部分Gα亚基的GTP酶活性，从而以依赖途径的方式作为负调节剂。在本综述中，我们总结了RGS蛋白在心脏代谢功能中的作用，重点关注它们的组织分布、作用机制以及在各种疾病状态下的失调情况。我们还讨论了靶向RGS蛋白治疗心脏代谢疾病的潜在治疗应用以及开发RGS调节剂的当前进展。相关文章：本文是主题为“G蛋白偶联受体的治疗靶点：澳大利亚临床与实验药理学家和毒理学家协会2021年虚拟年度科学会议的热点话题”特刊的一部分。要查看本节中的其他文章，请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc。
