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Distinct roles for ?-arrestin2 and arrestin-domain-containing proteins in ?2 adrenergic receptor trafficking.

ABSTRACT: ?-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 ?-arrestin in receptor regulation. We demonstrate that ?-arrestin2 is the primary adaptor that rapidly binds agonist-activated ?(2) adrenergic receptors (?(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 ?(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of ?-arrestin2. Rather, the role of ARRDC proteins is to traffic Nedd4-?(2)AR complexes to a subpopulation of early endosomes.

SUBMITTER: Han SO

PROVIDER: S-EPMC3596129 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Distinct roles for β-arrestin2 and arrestin-domain-containing proteins in β2 adrenergic receptor trafficking.

Han Sang-Oh SO Kommaddi Reddy P RP Shenoy Sudha K SK

EMBO reports 20121204 2

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, E ...[more]

PMID: 23208550

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