Gα s regulates the post-endocytic sorting of G protein-coupled receptors

Abstract

The role of Gα s in G protein-coupled receptor (GPCR) signalling at the cell surface is well established. Recent evidence has revealed the presence of Gα s on endosomes and its capacity to elicit GPCR-promoted signalling from this intracellular compartment. Here, we report an unconventional role for Gα s in the endocytic sorting of GPCRs to lysosomes. Cellular depletion of Gα s specifically delays the lysosomal degradation of GPCRs by disrupting the transfer of GPCRs into the intraluminal vesicles (ILVs) of multivesicular bodies. We show that Gα s interacts with GPCR-associated binding protein-1 (GASP1) and dysbindin, two key proteins that serve as linkers between GPCRs and the endosomal-sorting complex required for transport (ESCRT) machinery involved in receptor sorting into ILVs. Our findings reveal that Gα s plays a role in both GPCR signalling and trafficking pathways, providing another piece in the intertwining molecular network between these processes. © 2014 Macmillan Publishers Limited. All rights reserved.