Gαs regulates the post-endocytic sorting of G protein-coupled receptors

Stéphanie Rosciglione, Caroline Thériault, Marc-Olivier Boily, Marilène Paquette and Christine Lavoie ()
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Stéphanie Rosciglione: Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke
Caroline Thériault: Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke
Marc-Olivier Boily: Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke
Marilène Paquette: Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke
Christine Lavoie: Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract The role of Gαs in G protein-coupled receptor (GPCR) signalling at the cell surface is well established. Recent evidence has revealed the presence of Gαs on endosomes and its capacity to elicit GPCR-promoted signalling from this intracellular compartment. Here, we report an unconventional role for Gαs in the endocytic sorting of GPCRs to lysosomes. Cellular depletion of Gαs specifically delays the lysosomal degradation of GPCRs by disrupting the transfer of GPCRs into the intraluminal vesicles (ILVs) of multivesicular bodies. We show that Gαs 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 Gαs plays a role in both GPCR signalling and trafficking pathways, providing another piece in the intertwining molecular network between these processes.

Date: 2014
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DOI: 10.1038/ncomms5556

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