title: Arrestins: Critical Players in Trafficking of Many GPCRs.
abstract: Arrestins specifically bind active phosphorylated G protein-coupled receptors (GPCRs). Receptor binding induces the release of the arrestin C-tail, which in non-visual arrestins contains high-affinity binding sites for clathrin and its adaptor AP2. Thus, serving as a physical link between the receptor and key components of the internalization machinery of the coated pit is the best-characterized function of non-visual arrestins in GPCR trafficking. However, arrestins also regulate GPCR trafficking less directly by orchestrating their ubiquitination and deubiquitination. Several reports suggest that arrestins play additional roles in receptor trafficking. Non-visual arrestins appear to be required for the recycling of internalized GPCRs, and the mechanisms of their function in this case remain to be elucidated. Moreover, visual and non-visual arrestins were shown to directly bind N-ethylmaleimide-sensitive factor, an important ATPase involved in vesicle trafficking, but neither molecular details nor the biological role of these interactions is clear. Considering how many different proteins arrestins appear to bind, we can confidently expect the elucidation of additional trafficking-related functions of these versatile signaling adaptors.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA. Electronic address: vsevolod.gurevich@vanderbilt.edu.
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Gurevich
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Eugenia V
authors.initials: EV
authors.lastname: Gurevich
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D001665:Binding Sites; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D019390:Arrestins; D002966:Clathrin; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D043562:Receptors, G-Protein-Coupled; D025801:Ubiquitin; D000251:Adenosine Triphosphatases
keywords: Arrestin; GPCR; Internalization; Recycling; Signaling