Distinct roles for [beta]-arrestin2 and arrestin-domain-containing proteins in [beta]2 adrenergic receptor trafficking

• Published in: EMBO reports Vol. 14; no. 2; p. 164
• Main Authors: Han, Sang-oh, Kommaddi, Reddy P, Shenoy, Sudha K
• Format: Journal Article
• Language: English
• Published: Heidelberg Blackwell Publishing Ltd 01.02.2013
• Subjects: Endocytosis; Molecular biology; Proteins; Signal transduction
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2012.187

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. [PUBLICATION ABSTRACT]