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

EMBO Rep. 2013 Feb;14(2):164-71. doi: 10.1038/embor.2012.187. Epub 2012 Dec 4.


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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Animals
  • Arrestins / physiology*
  • COS Cells
  • Chlorocebus aethiops
  • Endocytosis
  • HEK293 Cells
  • Humans
  • Isoproterenol / pharmacology
  • Microscopy, Fluorescence
  • Models, Molecular
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Transport
  • Proteolysis
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Ubiquitination*
  • beta-Arrestin 1
  • beta-Arrestins


  • ARRB1 protein, human
  • ARRDC3 protein, human
  • Adrenergic beta-2 Receptor Agonists
  • Arrestins
  • Receptors, Adrenergic, beta-2
  • beta-Arrestin 1
  • beta-Arrestins
  • Isoproterenol