TY - JOUR
T1 - β-arrestin-dependent and-independent endosomal G protein activation by the vasopressin type 2 receptor
AU - Daly, Carole
AU - Guseinov, Akim Abdul
AU - Hahn, Hyunggu
AU - Tikhonova, Irina G.
AU - Thomsen, Alex Rojas Bie
AU - Plouffe, Bianca
N1 - Publisher Copyright:
© 2023, eLife Sciences Publications Ltd. All rights reserved.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.87754.1
DO - 10.7554/eLife.87754.1
M3 - Article
C2 - 37855711
AN - SCOPUS:85165394057
SN - 2050-084X
VL - 12
JO - eLife
JF - eLife
ER -