Document Detail


Distinct roles for β-arrestin2 and arrestin-domain-containing proteins in β2 adrenergic receptor trafficking.
MedLine Citation:
PMID:  23208550     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Sang-Oh Han; Reddy P Kommaddi; Sudha K Shenoy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-04
Journal Detail:
Title:  EMBO reports     Volume:  14     ISSN:  1469-3178     ISO Abbreviation:  EMBO Rep.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-07-22     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  100963049     Medline TA:  EMBO Rep     Country:  England    
Other Details:
Languages:  eng     Pagination:  164-71     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-2 Receptor Agonists / pharmacology
Animals
Arrestins / physiology*
COS Cells
Cercopithecus aethiops
Endocytosis
HEK293 Cells
Humans
Isoproterenol / pharmacology
Microscopy, Fluorescence
Models, Molecular
Protein Binding
Protein Interaction Domains and Motifs
Protein Transport
Proteolysis
Receptors, Adrenergic, beta-2 / metabolism*
Ubiquitination*
Grant Support
ID/Acronym/Agency:
HL 080525/HL/NHLBI NIH HHS; R01 HL080525/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/ARRDC3 protein, human; 0/Adrenergic beta-2 Receptor Agonists; 0/Arrestins; 0/Receptors, Adrenergic, beta-2; 0/beta-arrestin; L628TT009W/Isoproterenol
Comments/Corrections

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