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

Carole Daly; Akim Abdul  Guseinov; Hyunggu Hahn; Adam Wright; Irina G Tikhonova; Alex  Rojas Bie Thomsen; Bianca Plouffe

doi:10.7554/eLife.87754.3

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

Carole Daly, Akim Abdul Guseinov, Hyunggu Hahn, Adam Wright, Irina G Tikhonova, Alex Rojas Bie Thomsen^*, Bianca Plouffe^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

41 Downloads (Pure)

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 Gα_s and Gα_q/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 Gα_s activation, and thus, Gα_s-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 Gα_s, but also involves Gα_q/11. Furthermore, our data imply that β-arrestins potentiate Gα_s/Gα_q/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 language	English
Article number	RP87754
Number of pages	19
Journal	eLife
Volume	12
DOIs	https://doi.org/10.7554/eLife.87754.3
Publication status	Published - 19 Oct 2023

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10.7554/eLife.87754.3Licence: CC BY

β-arrestin-dependent and -independent endosomal G protein activation by the vasopressin type 2 receptor
Copyright 2023 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 4.94 MBLicence: CC BY

Investigation of the role of US28 subcellular location in the upregulation of oncomodulatory genes in the context of glioblastoma
Daly, C. (Author), Plouffe, B. (Supervisor), Evergren Mills, E. (Supervisor) & Taggart, C. (Supervisor), Dec 2023
Student thesis: Doctoral Thesis › Doctor of Philosophy

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@article{6c41ec4de16c4d6f8f2136db57dfb969,

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

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 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 imply 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.",

author = "Carole Daly and Guseinov, {Akim Abdul} and Hyunggu Hahn and Adam Wright and Tikhonova, {Irina G} and {Rojas Bie Thomsen}, Alex and Bianca Plouffe",

year = "2023",

month = oct,

day = "19",

doi = "10.7554/eLife.87754.3",

language = "English",

volume = "12",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

}

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 - Wright, Adam

AU - Tikhonova, Irina G

AU - Rojas Bie Thomsen, Alex

AU - Plouffe, Bianca

PY - 2023/10/19

Y1 - 2023/10/19

N2 - 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 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 imply 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 G protein-coupled receptor (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 imply 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.

U2 - 10.7554/eLife.87754.3

DO - 10.7554/eLife.87754.3

M3 - Article

SN - 2050-084X

VL - 12

JO - eLife

JF - eLife

M1 - RP87754

ER -

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

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Student theses

Investigation of the role of US28 subcellular location in the upregulation of oncomodulatory genes in the context of glioblastoma

Cite this