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

被引：92
作者：
Han, Sang-Oh [1 ]
Kommaddi, Reddy P. [1 ]
Shenoy, Sudha K. [1 ,2 ]
机构：
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA
来源：
EMBO REPORTS | 2013年 / 14卷 / 02期
基金：
美国国家卫生研究院;
关键词：
arrestin; adaptor; endocytosis; ubiquitin; Nedd4; BETA(2)-ADRENERGIC RECEPTOR; E3; LIGASE; UBIQUITINATION; ENDOCYTOSIS; CLATHRIN; NEDD4; RESENSITIZATION; DEGRADATION; ACTIVATION; RHODOPSIN;
D O I：
10.1038/embor.2012.187
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
beta-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 beta-arrestin in receptor regulation. We demonstrate that beta-arrestin2 is the primary adaptor that rapidly binds agonist-activated beta(2) adrenergic receptors (beta(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 beta(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of beta-arrestin2. Rather, the role of ARRDC proteins is to traffic Nedd4-beta(2)AR complexes to a subpopulation of early endosomes.
引用
收藏
页码：164 / 171
页数：8
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