title: Gαs regulates the post-endocytic sorting of G protein-coupled receptors.
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.
authors.affiliation: Department of Pharmacology, Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rosciglione
authors.affiliation: Department of Pharmacology, Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors.forename: Caroline
authors.initials: C
authors.lastname: Thériault
authors.affiliation: Department of Pharmacology, Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors.forename: Marc-Olivier
authors.initials: MO
authors.lastname: Boily
authors.affiliation: Department of Pharmacology, Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors.forename: Marilène
authors.initials: M
authors.lastname: Paquette
authors.affiliation: Department of Pharmacology, Institut de Pharmacologie de Sherbrooke, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors.forename: Christine
authors.initials: C
authors.lastname: Lavoie
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D044385:GTP-Binding Protein alpha Subunits; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C424444:WFIKKN2 protein, human
references.citation: Cell Signal. 2010 May;22(5):707-16
references.pmid: 19887105
references.citation: Stem Cells. 2004;22(6):1015-29
references.pmid: 15536192
references.citation: Science. 2005 Apr 22;308(5721):512-7
references.pmid: 15845844
references.citation: PLoS One. 2013;8(2):e56336
references.pmid: 23441177
references.citation: Science. 2002 Jul 26;297(5581):615-20
references.pmid: 12142540
references.citation: J Cell Sci. 2003 Oct 15;116(Pt 20):4169-79
references.pmid: 12953068
references.citation: J Cell Biol. 2002 Apr 1;157(1):91-101
references.pmid: 11916981
references.citation: J Biol Chem. 2010 Apr 30;285(18):13990-4004
references.pmid: 20159979
references.citation: J Cell Biol. 2012 Apr 30;197(3):407-19
references.pmid: 22547407
references.citation: Biochim Biophys Acta. 1998 Aug 14;1404(1-2):161-71
references.pmid: 9714787
references.citation: J Biol Chem. 1994 May 27;269(21):14919-23
references.pmid: 8195123
references.citation: J Biol Chem. 2007 Oct 5;282(40):29646-57
references.pmid: 17675298
references.citation: EMBO J. 2012 Jun 29;31(13):2869-81
references.pmid: 22580821
references.citation: J Biol Chem. 2001 Apr 13;276(15):12345-55
references.pmid: 11152677
references.citation: Mol Biol Cell. 1992 Dec;3(12):1317-28
references.pmid: 1493332
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14961-6
references.pmid: 11752444
references.citation: Biochem Biophys Res Commun. 1996 Jan 5;218(1):383-9
references.pmid: 8573166
references.citation: Science. 2000 Nov 24;290(5496):1574-7
references.pmid: 11090355
references.citation: PLoS One. 2010 Feb 19;5(2):e9325
references.pmid: 20174469
references.citation: Dev Cell. 2003 Nov;5(5):709-22
references.pmid: 14602072
references.citation: Genome Res. 2005 Mar;15(3):376-84
references.pmid: 15710747
references.citation: J Biol Chem. 2013 Sep 27;288(39):27849-60
references.pmid: 23935101
references.citation: J Biol Chem. 1993 Dec 5;268(34):25824-35
references.pmid: 8245019
references.citation: PLoS Biol. 2009 Aug;7(8):e1000172
references.pmid: 19688034
references.citation: Cell. 1994 Jul 1;77(7):1063-70
references.pmid: 7912657
references.citation: J Biol Chem. 2004 Dec 24;279(52):54291-303
references.pmid: 15452121
references.citation: Annu Rev Pharmacol Toxicol. 2009;49:31-56
references.pmid: 18834311
references.citation: J Biol Chem. 2004 May 21;279(21):22522-31
references.pmid: 15024011
references.citation: Mol Biol Cell. 1996 Aug;7(8):1225-33
references.pmid: 8856666
references.citation: Cell Signal. 2010 Aug;22(8):1254-66
references.pmid: 20403427
references.citation: Br J Pharmacol. 2013 Mar;168(6):1355-74
references.pmid: 23082996
references.citation: FEBS Lett. 1996 Jun 24;389(1):61-5
references.pmid: 8682207
references.citation: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3135-9
references.pmid: 1849644
references.citation: J Biol Chem. 1998 Jan 9;273(2):685-8
references.pmid: 9422717
references.citation: Annu Rev Pharmacol Toxicol. 2008;48:537-68
references.pmid: 18184106
references.citation: J Biol Chem. 1993 Nov 15;268(32):23769-72
references.pmid: 8226908
references.citation: Science. 1992 Mar 27;255(5052):1695-7
references.pmid: 1348148
references.citation: Pharmacol Rev. 2013 Feb 13;65(2):545-77
references.pmid: 23406670
references.citation: Mol Biol Cell. 2002 Jun;13(6):1965-76
references.pmid: 12058063
references.citation: Nature. 2010 Apr 8;464(7290):864-9
references.pmid: 20305637
references.citation: Nat Chem Biol. 2009 Oct;5(10):734-42
references.pmid: 19701185
references.citation: Cell Signal. 2012 Jan;24(1):25-34
references.pmid: 21907280
references.citation: Mol Biol Cell. 2012 Dec;23(23):4623-34
references.pmid: 23051738
references.citation: Mol Pharmacol. 2005 May;67(5):1493-504
references.pmid: 15703379
references.citation: Mol Pharmacol. 1993 Aug;44(2):255-63
references.pmid: 8394989
references.citation: Mol Biol Cell. 2012 Sep;23(18):3612-23
references.pmid: 22833563
references.citation: J Biol Chem. 2004 Oct 15;279(42):44101-12
references.pmid: 15297467
references.citation: J Biol Chem. 2011 Nov 18;286(46):40193-204
references.pmid: 21953467
references.citation: Traffic. 2011 Feb;12(2):170-84
references.pmid: 21106040
references.citation: Eur J Immunol. 1997 Aug;27(8):2102-12
references.pmid: 9295051
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3178-83
references.pmid: 19211784
references.citation: J Cell Sci. 2001 Jun;114(Pt 12):2255-63
references.pmid: 11493665
references.citation: J Neurochem. 2004 May;89(3):766-75
references.pmid: 15086532
references.citation: BMC Physiol. 2004 Jan 07;4:1
references.pmid: 14711382
references.citation: J Biol Chem. 2011 Nov 25;286(47):40802-13
references.pmid: 21990357
references.citation: DNA Cell Biol. 2000 Apr;19(4):195-204
references.pmid: 10798443
references.citation: Arch Biochem Biophys. 1995 Mar 10;317(2):337-42
references.pmid: 7893147
references.citation: Am J Physiol Cell Physiol. 2002 Aug;283(2):C383-5
references.pmid: 12107046
references.citation: Mol Pharmacol. 2002 Feb;61(2):352-9
references.pmid: 11809860
references.citation: Mol Pharmacol. 1994 May;45(5):997-1003
references.pmid: 8190115
references.citation: Mol Biol Cell. 2004 Dec;15(12):5538-50
references.pmid: 15469987
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11906-11
references.pmid: 21730137
references.citation: J Biol Chem. 2011 Jan 14;286(2):1598-608
references.pmid: 21030592
references.citation: Nature. 2013 Mar 28;495(7442):534-8
references.pmid: 23515162
references.citation: J Biol Chem. 2002 Jun 7;277(23):21080-5
references.pmid: 11927592
references.citation: J Biol Chem. 2010 Oct 15;285(42):32393-404
references.pmid: 20720014
references.citation: Neuron. 2011 Jul 28;71(2):278-90
references.pmid: 21791287
references.citation: Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2800-4
references.pmid: 8146194
references.citation: Cancer Sci. 2007 Mar;98(3):373-9
references.pmid: 17270027
references.citation: J Microsc. 1993 Mar;169(3):375-382
references.pmid: 33930978