Role of the V2R-βarrestin-Gβγ complex in promoting G protein translocation to endosomes.

ABSTRACT: Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαβγ proteins, followed by the recruitment of GPCR kinases and βarrestin (βarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both βarr and Gβγ contribute to such non-canonical endosomal G protein signaling, but their specific roles and contributions remain poorly understood. Here, we demonstrate that the vasopressin V₂ receptor (V₂R)-βarr complex scaffolds Gβγ at the plasma membrane through a direct interaction with βarr, enabling its transport to endosomes. Gβγ subsequently potentiates Gα_s

SUBMITTER: Sokrat B 

PROVIDER: S-EPMC11228049 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature