< em > β < /em > -Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

Pharmacol Rev. 2023 Sep;75(5):854-884. doi: 10.1124/pharmrev.121.000302. Epub 2023 Apr 7.ABSTRACTThe two β-arrestins, β-arrestin-1 and -2 (systematic names: arrestin-2 and -3, respectively), are multifunctional intracellular proteins that regulate the activity of a very large number of cellular signaling pathways and physiologic functions. The two proteins were discovered for their ability to disrupt signaling via G protein-coupled receptors (GPCRs) via binding to the activated receptors. However, it is now well recognized that both β-arrestins can also act as direct modulators of numerous cellular processes via either GPCR-dependent or -independent mechanisms. Recent structural, biophysical, and biochemical studies have provided novel insights into how β-arrestins bind to activated GPCRs and downstream effector proteins. Studies with β-arrestin mutant mice have identified numerous physiologic and pathophysiological processes regulated by β-arrestin-1 and/or -2. Following a short summary of recent structural studies, this review primarily focuses on β-arrestin-regulated physiologic functions, with particular focus on the central nervous system and the roles of β-arrestins in carcinogenesis and key metabolic processes including the maintenance of glucose and energy homeostasis. This review also highlights potential therapeutic implications of these studies and discusses strategies that could prove useful for targeting specific β-arrestin-regulated signaling pathways f...
Source: Pharmacognosy Reviews - Category: Drugs & Pharmacology Authors: Source Type: research