Emerging Functional Divergence of β-Arrestin Isoforms in GPCR Function

Trends Endocrinol Metab. 2015 Nov;26(11):628-642. doi: 10.1016/j.tem.2015.09.001. Epub 2015 Oct 21.


G protein-coupled receptors (GPCRs) are tightly regulated by multifunctional protein β-arrestins. Two isoforms of β-arrestin sharing more than 70% sequence identity and overall very similar 3D structures, β-arrestins 1 and 2, were originally expected to be functionally redundant. However, in recent years multiple lines of emerging evidence suggest they have distinct roles in various aspects of GPCR regulation and signaling. We summarize selected examples of GPCRs where β-arrestin isoforms are discovered to display non-overlapping and sometimes even antagonistic functions. We also discuss potential mechanistic basis for their functional divergence and highlight new frontiers that are likely to form the focal points of research in this area in coming years.

Keywords: G protein-coupled receptors; arrestin; biased agonism; cellular signaling; desensitization; mitogen-activated protein kinase..

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arrestins / metabolism
  • Arrestins / physiology*
  • Humans
  • Protein Isoforms
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*
  • beta-Arrestins


  • Arrestins
  • Protein Isoforms
  • Receptors, G-Protein-Coupled
  • beta-Arrestins