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Noncanonical scaffolding of G αi and β-arrestin by G protein-coupled receptors.

Authors :
Smith JS
Pack TF
Inoue A
Lee C
Zheng K
Choi I
Eiger DS
Warman A
Xiong X
Ma Z
Viswanathan G
Levitan IM
Rochelle LK
Staus DP
Snyder JC
Kahsai AW
Caron MG
Rajagopal S
Source :
Science (New York, N.Y.) [Science] 2021 Mar 12; Vol. 371 (6534). Date of Electronic Publication: 2021 Jan 21.
Publication Year :
2021

Abstract

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific G <subscript>α</subscript> protein subtypes and β-arrestin adaptor proteins. G protein-mediated signaling and β-arrestin-mediated signaling have been considered separable. We show here that GPCRs promote a direct interaction between G <subscript>αi</subscript> protein subtype family members and β-arrestins regardless of their canonical G <subscript>α</subscript> protein subtype coupling. G <subscript>αi</subscript> :β-arrestin complexes bound extracellular signal-regulated kinase (ERK), and their disruption impaired both ERK activation and cell migration, which is consistent with β-arrestins requiring a functional interaction with G <subscript>αi</subscript> for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of G <subscript>αi</subscript> :β-arrestin signaling complexes.<br /> (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Details

Language :
English
ISSN :
1095-9203
Volume :
371
Issue :
6534
Database :
MEDLINE
Journal :
Science (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
33479120
Full Text :
https://doi.org/10.1126/science.aay1833