Journal Article

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

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

2023

Overview

The vasopressin type 2 receptor (V 2 R) is an essential G protein-coupled receptor (GPCR) in renal regulation of water homeostasis. Upon stimulation, the V 2 R 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 V 2 R does not terminate Gα s activation, and thus, Gα s -mediated signaling is sustained while the receptor is internalized. Here, we demonstrate that this V 2 R 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 V 2 R 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.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Arrestin / Arrestins - metabolism / beta-Arrestin 1 - metabolism / beta-Arrestins - metabolism / Bioluminescence / Biosensors / Cell Biology / endosomal signaling / Endosomes / Endosomes - metabolism / Experiments / G protein-coupled receptors / G proteins / GTP-Binding Proteins - metabolism / Homeostasis / Internalization / Kinases / megaplex / Physiology / Plasma / Proteins / Receptors, Vasopressin / Variance analysis / Vasopressin / vasopressin type 2 receptor / Vasopressin V2 receptors / Vasopressins - metabolism