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Updated: Jun 21, 2025

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
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Role of the V2R-βarrestin-Gβγ complex in promoting G protein translocation to endosomes

Badr Sokrat1,2,3, Anthony H Nguyen4, Alex R B Thomsen4,5,3

  • 1Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC, H3T 1J4, Canada.

Communications Biology
|July 7, 2024
PubMed

Insights

G protein-coupled receptors (GPCRs) signal from endosomes. This study shows βarrestin scaffolds Gβγ for endosomal transport, enabling sustained G protein signaling.

Area of Science:

  • Cell Biology
  • Molecular Pharmacology
  • Biochemistry

Background:

  • G protein-coupled receptors (GPCRs) classically signal from the plasma membrane.
  • Some GPCRs mediate distinct cellular responses through signaling from internalized endosomal compartments.
  • The roles of βarrestin (βarr) and Gβγ in endosomal GPCR signaling are not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of non-canonical endosomal G protein signaling.
  • To investigate the specific roles of βarrestin and Gβγ in vasopressin V2 receptor (V2R) signaling.
  • To understand how G protein subunits are transported to endosomes.

Main Methods:

  • Investigated the interaction between V2R, βarrestin, and Gβγ.
  • Utilized techniques to track protein translocation from plasma membrane to endosomes.
  • Assessed the impact of βarrestin and Gβγ on Gαs endosomal localization.

Main Results:

  • Demonstrated that the V2R-βarrestin complex directly scaffolds Gβγ at the plasma membrane.
  • Showed that βarrestin facilitates Gβγ transport to endosomes.
  • Revealed that Gβγ potentiates Gαs translocation to endosomes, potentially regenerating Gs signaling pools.

Conclusions:

  • βarrestin acts as a scaffold to facilitate Gβγ transport to endosomes for sustained GPCR signaling.
  • This mechanism explains the translocation of G protein subunits to endosomal compartments.
  • Provides a foundation for understanding βarrestin's role in mediating prolonged G protein signaling from endosomes.

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