Role of the V2R-ßarrestin-Gßγ complex in promoting G protein translocation to endosomes.
Commun Biol
; 7(1): 826, 2024 Jul 07.
Article
in En
| MEDLINE
| ID: mdl-38972875
ABSTRACT
Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαßγ proteins, followed by the recruitment of GPCR kinases and ßarrestin (ßarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both ßarr and Gßγ 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)-ßarr complex scaffolds Gßγ at the plasma membrane through a direct interaction with ßarr, enabling its transport to endosomes. Gßγ subsequently potentiates Gαs endosomal translocation, presumably to regenerate an endosomal pool of heterotrimeric Gs. This work shines light on the mechanism underlying G protein subunits translocation from the plasma membrane to the endosomes and provides a basis for understanding the role of ßarr in mediating sustained G protein signaling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endosomes
/
Receptors, Vasopressin
/
Protein Transport
/
GTP-Binding Protein beta Subunits
/
GTP-Binding Protein gamma Subunits
/
Beta-Arrestins
Limits:
Humans
Language:
En
Journal:
Commun Biol
Year:
2024
Type:
Article
Affiliation country:
Canada