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Distinct roles for β‐arrestin2 and arrestin‐domain‐containing proteins in β 2 adrenergic receptor trafficking
Author(s) -
Han SangOh,
Kommaddi Reddy P,
Shenoy Sudha K
Publication year - 2013
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.187
Subject(s) - arrestin , signal transducing adaptor protein , microbiology and biotechnology , endosome , ubiquitin ligase , internalization , nedd4 , clathrin , endocytic cycle , biology , receptor , endocytosis , ubiquitin , chemistry , signal transduction , g protein coupled receptor , biochemistry , intracellular , gene
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.