title: Emerging Functional Divergence of β-Arrestin Isoforms in GPCR Function.
abstract: 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.
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
authors.forename: Bhagyashri
authors.initials: B
authors.lastname: Gupta
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India.
authors.forename: Charu
authors.initials: C
authors.lastname: Gupta
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India. Electronic address: arshukla@iitk.ac.in.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Shukla
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins
keywords: G protein-coupled receptors; arrestin; biased agonism; cellular signaling; desensitization; mitogen-activated protein kinase.