Abstract
ß-arrestins are multifunctional proteins that modulate heptahelical 7 transmembrane receptors, also known as G protein-coupled receptors (GPCRs), a superfamily of receptors that regulate most physiological processes. ß-arrestin modulation of GPCR function includes termination of G protein-dependent signaling, initiation of ß-arrestin-dependent signaling, receptor trafficking to degradative or recycling pathways, receptor transactivation, transcriptional regulation, and localization of second messenger regulators. The pleiotropic influence ß-arrestins exert on these receptors regulates a breadth of physiological functions, and additionally, ß-arrestins are involved in the pathophysiology of numerous and wide-ranging diseases, making them prime therapeutic targets. In this review, we briefly describe the mechanisms by which ß-arrestins regulate GPCR signaling, including the functional cellular mechanisms modulated by ß-arrestins and relate this to observed pathophysiological responses associated with ß-arrestins. We focus on the role for ß-arrestins in transducing cell signaling; a pathway that is complementary to the classical G protein-coupling pathway. The existence of these GPCR dual signaling pathways offers an immense therapeutic opportunity through selective targeting of one signaling pathway over the other. Finally, we will consider several mechanisms by which the potential of dual signaling pathway regulation can be harnessed and the implications for improved disease treatments.
Highlights
We briefly describe the mechanisms by which ß-arrestins regulate G protein-coupled receptors (GPCRs) signaling, including the functional cellular mechanisms modulated by ß-arrestins and relate this to observed pathophysiological responses associated with ß-arrestins
We focus on the role for ß-arrestins in transducing cell signaling; a pathway that is complementary to the classical G protein-coupling pathway
The beta prefix is because their first documented receptor substrate was the ß2-adrenergic receptor (ß2AR) and the “arrestin” term was because their major function is in terminating signaling via G proteins (Benovic et al, 1987). ß-arrestin proteins have functional and structural domains that allow them to bind to receptors as well as biochemical intermediates, events that are key to their function (Shenoy and Lefkowitz, 2011; Peterson and Luttrell, 2017)
Summary
We briefly describe the mechanisms by which ß-arrestins regulate GPCR signaling, including the functional cellular mechanisms modulated by ß-arrestins and relate this to observed pathophysiological responses associated with ß-arrestins. These GPCRs are a very important class of receptor since they mediate almost all physiological processes, and their signaling is the target of roughly 40% of all prescribed drugs (Wise et al, 2002).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.