title: Distinct roles for β-arrestin2 and arrestin-domain-containing proteins in β2 adrenergic receptor trafficking.
abstract: β-arrestin 1 and 2 (also known as arrestin 2 and 3) are homologous adaptor proteins that regulate seven-transmembrane receptor trafficking and signalling. Other proteins with predicted 'arrestin-like' structural domains but lacking sequence homology have been indicated to function like β-arrestin in receptor regulation. We demonstrate that β-arrestin2 is the primary adaptor that rapidly binds agonist-activated β(2) adrenergic receptors (β(2)ARs) and promotes clathrin-dependent internalization, E3 ligase Nedd4 recruitment and ubiquitin-dependent lysosomal degradation of the receptor. The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized β(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of β-arrestin2. Rather, the role of ARRDC proteins is to traffic Nedd4-β(2)AR complexes to a subpopulation of early endosomes.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Sang-Oh
authors.initials: SO
authors.lastname: Han
authors.forename: Reddy P
authors.initials: RP
authors.lastname: Kommaddi
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Shenoy
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D019390:Arrestins / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004705:Endocytosis; D057809:HEK293 Cells; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D059748:Proteolysis; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D054875:Ubiquitination; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605253:ARRB1 protein, human; C508469:ARRDC3 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D019390:Arrestins; D018343:Receptors, Adrenergic, beta-2; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D007545:Isoproterenol