title: Regulation of GPCR Trafficking by Ubiquitin.
abstract: G protein-coupled receptor (GPCR)-promoted signaling mediates cellular responses to a variety of stimuli involved in diverse physiological processes. In addition, GPCRs are also the largest class of target for many drugs used to treat a variety of diseases. Despite the role of GPCR signaling in health and disease, the molecular mechanisms governing GPCR signaling remain poorly understanding. Classically, GPCR signaling is tightly regulated by GPCR kinases and β-arrestins, which act in a concerted fashion to govern GPCR desensitization and also GPCR trafficking. Ubiquitination has now emerged as an important posttranslational modification that has multiple roles, either directly or indirectly, in governing GPCR trafficking. Recent studies have revealed a mechanistic link between GPCR phosphorylation, β-arrestins, and ubiquitination. Here, we review recent developments in our understanding of how ubiquitin regulates GPCR trafficking within the endocytic pathway.
authors.affiliation: Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Health Sciences Division, Maywood, Illinois, USA.
authors.forename: Justine E
authors.initials: JE
authors.lastname: Kennedy
authors.affiliation: Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Health Sciences Division, Maywood, Illinois, USA. Electronic address: amarchese@luc.edu.
authors.forename: Adriano
authors.initials: A
authors.lastname: Marchese
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D043562:Receptors, G-Protein-Coupled; D025801:Ubiquitin; D000071557:beta-Arrestins
keywords: CXCR4; Degradation; ESCRT; Endosomal sorting; Endosome; GPCR; Lysosome; Multivesicular body; Receptor trafficking; Ubiquitin