RT Journal Article
SR Electronic
T1 Noncanonical scaffolding of G<sub>αi</sub> and β-arrestin by G protein-coupled receptors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 629576
DO 10.1101/629576
A1 Jeffrey S. Smith
A1 Thomas F. Pack
A1 Asuka Inoue
A1 Claudia Lee
A1 Xinyu Xiong
A1 Kevin Zheng
A1 Alem W. Kahsai
A1 Issac Choi
A1 Zhiyuan Ma
A1 Ian M. Levitan
A1 Lauren K. Rochelle
A1 Dean P. Staus
A1 Joshua C. Snyder
A1 Marc G. Caron
A1 Sudarshan Rajagopal
YR 2019
UL http://biorxiv.org/content/early/2019/05/07/629576.abstract
AB G-protein-coupled receptors (GPCRs) enable cells to sense and respond appropriately to hormonal and environmental signals, and are a target of ~30% of all FDA-approved medications. Canonically, each GPCR couples to distinct Gα proteins, such as Gαs, Gαi, Gαq or Gα12/13, as well as β-arrestins. These transducer proteins translate and integrate extracellular stimuli sensed by GPCRs into intracellular signals through what are broadly considered separable signalling pathways. However, the ability of Gα proteins to directly interact with β-arrestins to integrate signalling has not previously been appreciated. Here we show a novel interaction between Gαi protein family members and β-arrestin. Gαi:β-arrestin complexes were formed by all GPCRs tested, regardless of their canonical G protein isoform coupling, and could bind both GPCRs as well as the extracellular signal-regulated kinase (ERK). This novel paradigm of Gαi:β-arrestin scaffolds enhances our understanding of GPCR signalling.