We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
β-Arrestin-dependent and -independent endosomal G protein activation by the vasopressin type 2 receptor.
- Authors
Daly, Carole; Guseinov, Akim Abdul; Hyunggu Hahn; Wright, Adam; Tikhonova, Irina G.; Thomsen, Alex Rojas Bie; Plouffe, Bianca
- Abstract
The vasopressin type 2 receptor (V2R) is an essential G protein-coupled receptor (GPCR) in renal regulation of water homeostasis. Upon stimulation, the V2R activates Gas and Gaq/11, which is followed by robust recruitment of ß-arrestins and receptor internalization into endosomes. Unlike canonical GPCR signaling, the ß-arrestin association with the V2R does not terminate Gas activation, and thus, Gas-mediated signaling is sustained while the receptor is internalized. Here, we demonstrate that this V2R ability to co-interact with G protein/ß-arrestin and promote endosomal G protein signaling is not restricted to Gas, but also involves Gaq/11. Furthermore, our data imply that ß-arrestins potentiate Gas/Gaq/11 activation at endosomes rather than terminating their signaling. Surprisingly, we found that the V2R internalizes and promote endosomal G protein activation independent of ß-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 ß-arrestin-dependent and -independent manners.
- Subjects
ARRESTINS; G protein coupled receptors; G proteins; VASOPRESSIN; ENDOSOMES
- Publication
eLife, 2023, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.87754