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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Han, S-O; Kommaddi, RP; Shenoy, SK

Published Date

  • February 2013

Published In

Volume / Issue

  • 14 / 2

Start / End Page

  • 164 - 171

PubMed ID

  • 23208550

Pubmed Central ID

  • 23208550

Electronic International Standard Serial Number (EISSN)

  • 1469-3178

Digital Object Identifier (DOI)

  • 10.1038/embor.2012.187

Language

  • eng

Conference Location

  • England