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Noncanonical interactions of G proteins and β‐arrestins: from competitors to companions
Author(s) -
Smith Jeffrey S.,
Pack Thomas F.
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15749
Subject(s) - g protein coupled receptor , arrestin , signal transducing adaptor protein , g protein , microbiology and biotechnology , signal transduction , gtpase activating protein , biology , protein–protein interaction , gq alpha subunit , cell signaling , chemistry
G protein‐coupled receptors (GPCRs) canonically couple to specific Gα protein subtypes and β‐arrestin adaptor proteins to initiate cellular signaling events. G protein‐mediated signaling and β‐arrestin‐mediated signaling have broadly been considered separable. However, noncanonical interactions between G proteins and GPCRs are now appreciated that do not result in nucleotide exchange and classical G protein signaling. New findings also demonstrate direct interactions between G proteins and β‐arrestins that are required for certain signaling and physiological events. Further adding to the intrigue of these newly appreciated G protein:β‐arrestin complexes, only the Gαi subtype family members, and not Gαs, Gαq/11, or Gα12/13 subtypes, appear to form direct interactions with β‐arrestin. Here, we review the recent discovery and initial characterization of G protein:β‐arrestin complexes and describe how these complexes provide mechanistic insight into seemingly disparate observations. G protein:β‐arrestin complexes build upon other observations of noncanonical G protein and β‐arrestin signaling events to add an additional dimension to our understanding of GPCR signaling.