The roles of RGS proteins in cardiometabolic disease

Abstract

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.

Highlights and hot topics in GPCR research from ‘Down Under’

“…While the cross-talk is reproducible, it remains to be confirmed whether it occurs at the receptor level (i.e., dimerisation/oligomerisation) or further downstream. Indeed, McNeill and Zhao (2024) describe a family of downstream regulators of GPCR signalling, called regulator of G protein signalling (RGS) proteins, that have been implicated in cardiometabolic disorders. They argue that tissue-specific expression and selectivity for Gα protein subtypes makes the RGS family of intracellular proteins exciting therapeutic targets.…”