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

Journal Article (Journal Article)

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific Gα 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 Gαi protein subtype family members and β-arrestins regardless of their canonical Gα protein subtype coupling. Gαi: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 Gαi for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of Gαi:β-arrestin signaling complexes.

Full Text

Duke Authors

Cited 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

Published Date

  • March 12, 2021

Published In

Volume / Issue

  • 371 / 6534

PubMed ID

  • 33479120

Pubmed Central ID

  • 33479120

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aay1833


  • eng

Conference Location

  • United States