β-arrestin-dependent and-independent endosomal G protein activation by the vasopressin type 2 receptor

Carole Daly, Akim Abdul Guseinov, Hyunggu Hahn, Irina G. Tikhonova, Alex Rojas Bie Thomsen, Bianca Plouffe

Research output: Contribution to journalArticlepeer-review

Abstract

The vasopressin type 2 receptor (V2R) is an essential GPCR in renal regulation of water homeostasis. Upon stimulation, the V2R activates Gαs and Gαq/11, which is followed by robust recruitment of β-arrestins and receptor internalization into endosomes. Unlike canonical GPCR signaling, the β-arrestin association with the V2R does not terminate Gαs activation, and thus, Gαs-mediated signaling is sustained while the receptor is internalized. Here, we demonstrate that this V2R ability to co-interact with G protein/β-arrestin and promote endosomal G protein signaling is not restricted to Gαs, but also involves Gαq/11. Furthermore, our data implies that β-arrestins potentiate Gαs/Gαq/11 activation at endosomes rather than terminating their signaling. Surprisingly, we found that the V2R internalizes and promote endosomal G protein activation independent of β-arrestins to a minor degree. These new observations challenge the current model of endosomal GPCR signaling and suggest that this event can occur in both β-arrestin-dependent and-independent manners.

Original languageEnglish (US)
JournaleLife
Volume12
DOIs
StatePublished - 2023

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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