title: Ubiquitin-Related Roles of β-Arrestins in Endocytic Trafficking and Signal Transduction.
abstract: The non-visual arrestins, β-arrestin1, and β-arrestin2 were originally identified as proteins that bind to seven-transmembrane receptors (7TMRs, also called G protein-coupled receptors, GPCRs) and block heterotrimeric G protein activation, thus leading to desensitization of transmembrane signaling. However, as subsequent discoveries have continually demonstrated, their functionality is not constrained to desensitization. They are now recognized for their critical roles in mediating intracellular trafficking of 7TMRs, growth factor receptors, ion transporters, ion channels, nuclear receptors, and non-receptor proteins. Additionally, they function as crucial mediators of ubiquitination of 7TMRs as well as other receptors and non-receptor proteins. Recently, emerging studies suggest that a class of proteins with predicted structural features of β-arrestins regulate substrate ubiquitination in yeast and higher mammals, lending support to the idea that the adaptor role of β-arrestins in protein ubiquitination is evolutionarily conserved. β-arrestins also function as scaffolds for kinases and transduce signals from 7TMRs through pathways that do not require G protein activation. Remarkably, the endocytic and scaffolding functions of β-arrestin are intertwined with its ubiquitination status; the dynamic and site specific ubiquitination on β-arrestin plays a critical role in stabilizing β-arrestin-7TMR association and the formation of signalosomes. This review summarizes the current findings on ubiquitin-dependent regulation of 7TMRs as well as β-arrestins and the potential role of reversible ubiquitination as a "biological switch" in signal transduction. J. Cell. Physiol. 231: 2071-2080, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Jean-Charles
authors.affiliation: Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina.
authors.forename: Vishwaesh
authors.initials: V
authors.lastname: Rajiv
authors.affiliation: Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina.|Department of Cell Biology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Shenoy
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D021381:Protein Transport / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology; D000071557:beta-Arrestins / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D000071557:beta-Arrestins