Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 10 2022
26 10 2022
Historique:
received:
21
07
2021
accepted:
11
10
2022
entrez:
26
10
2022
pubmed:
27
10
2022
medline:
29
10
2022
Statut:
epublish
Résumé
G protein-coupled receptors (GPCRs) are important drug targets that mediate various signaling pathways by activating G proteins and engaging β-arrestin proteins. Despite its importance for the development of therapeutics with fewer side effects, the underlying mechanism that controls the balance between these signaling modes of GPCRs remains largely unclear. Here, we show that assembly into dimers and oligomers can largely influence the signaling mode of the platelet-activating factor receptor (PAFR). Single-particle analysis results show that PAFR can form oligomers at low densities through two possible dimer interfaces. Stabilization of PAFR oligomers through cross-linking increases G protein activity, and decreases β-arrestin recruitment and agonist-induced internalization significantly. Reciprocally, β-arrestin prevents PAFR oligomerization. Our results highlight a mechanism involved in the control of receptor signaling, and thereby provide important insights into the relationship between GPCR oligomerization and downstream signaling.
Identifiants
pubmed: 36289206
doi: 10.1038/s41467-022-34056-4
pii: 10.1038/s41467-022-34056-4
pmc: PMC9606269
doi:
Substances chimiques
Platelet Activating Factor
0
Receptors, G-Protein-Coupled
0
beta-Arrestins
0
beta-Arrestin 1
0
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6365Informations de copyright
© 2022. The Author(s).
Références
Nature. 2021 Jun;594(7864):594-598
pubmed: 33911284
Pharmacol Ther. 2007 Sep;115(3):410-8
pubmed: 17655934
J Biol Chem. 2010 Feb 26;285(9):6337-47
pubmed: 20026606
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12199-204
pubmed: 17620610
Physiol Rev. 2000 Oct;80(4):1291-335
pubmed: 11015615
Nat Commun. 2019 Jun 24;10(1):2765
pubmed: 31235691
Sci Signal. 2012 Nov 20;5(251):pe51
pubmed: 23169816
Trends Biochem Sci. 2014 Dec;39(12):594-602
pubmed: 25458114
Pharmacol Rev. 2014 Feb 10;66(2):413-34
pubmed: 24515647
J Biol Chem. 2002 Jan 18;277(3):2247-57
pubmed: 11698401
Signal Transduct Target Ther. 2021 Jan 8;6(1):7
pubmed: 33414387
Trends Cell Biol. 2020 Sep;30(9):736-747
pubmed: 32622699
Infect Immun. 2005 Dec;73(12):7827-35
pubmed: 16299272
Curr Opin Cell Biol. 2014 Apr;27:78-86
pubmed: 24480089
Trends Pharmacol Sci. 2021 Apr;42(4):283-299
pubmed: 33581873
Nature. 2021 Jul;595(7867):450-454
pubmed: 34194039
Nat Chem Biol. 2015 Feb;11(2):134-40
pubmed: 25503927
EMBO J. 2005 Feb 9;24(3):499-509
pubmed: 15660124
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3684-9
pubmed: 10725388
Trends Pharmacol Sci. 2011 Sep;32(9):521-33
pubmed: 21680031
Nature. 2017 Jan 19;541(7637):421-424
pubmed: 28077870
Molecules. 2021 Feb 06;26(4):
pubmed: 33561962
Cell Res. 2016 Aug;26(8):935-45
pubmed: 27174053
Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):29144-29154
pubmed: 33148803
J Lab Clin Med. 2006 Jun;147(6):281-9
pubmed: 16750665
Mol Pharmacol. 2013 Jul;84(1):158-69
pubmed: 23632086
Nat Commun. 2016 Oct 03;7:12832
pubmed: 27694816
Nat Chem Biol. 2017 Aug 18;13(9):929-937
pubmed: 28820879
Curr Opin Pharmacol. 2010 Feb;10(1):23-9
pubmed: 19850521
Eur J Pharmacol. 1997 Apr 23;325(1):69-80
pubmed: 9151941
Drug Discov Today. 2018 Sep;23(9):1591-1595
pubmed: 29649573
Trends Pharmacol Sci. 2018 Jul;39(7):672-684
pubmed: 29739625
Annu Rev Pharmacol Toxicol. 2002;42:409-35
pubmed: 11807178
Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):743-8
pubmed: 23267088
J Biol Chem. 2007 Apr 6;282(14):10576-84
pubmed: 17283075
Mol Pharmacol. 2018 Apr;93(4):259-265
pubmed: 29326242
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):E1416-25
pubmed: 23487753
Nat Commun. 2012;3:995
pubmed: 22871814
Sci Signal. 2018 Sep 25;11(549):
pubmed: 30254056
FASEB J. 2014 Aug;28(8):3734-44
pubmed: 24830383
EMBO J. 2011 May 06;30(12):2336-49
pubmed: 21552208
Curr Opin Pharmacol. 2010 Feb;10(1):6-13
pubmed: 19962942
Elife. 2017 Aug 10;6:
pubmed: 28829739
Pharmacol Rev. 2019 Apr;71(2):267-315
pubmed: 30914442
Cell. 2018 Jan 11;172(1-2):41-54.e19
pubmed: 29249361
Nat Commun. 2019 May 20;10(1):2234
pubmed: 31110175
EMBO J. 2006 Dec 13;25(24):5693-702
pubmed: 17139258
J Pharmacol Exp Ther. 2011 Feb;336(2):296-302
pubmed: 21030484
Elife. 2019 Jun 07;8:
pubmed: 31172948
ACS Chem Biol. 2020 Sep 18;15(9):2577-2587
pubmed: 32808756
Nat Rev Drug Discov. 2018 Apr;17(4):243-260
pubmed: 29302067
Sci Rep. 2017 Dec 4;7(1):16873
pubmed: 29203889
Front Endocrinol (Lausanne). 2015 Nov 09;6:167
pubmed: 26617570
EMBO J. 2008 Sep 3;27(17):2293-304
pubmed: 18668123
Mol Cell. 2021 Oct 21;81(20):4165-4175.e6
pubmed: 34433090
Mol Neurobiol. 2017 Sep;54(7):5563-5572
pubmed: 27613281
Nature. 1997 Nov 6;390(6655):88-91
pubmed: 9363896
Nat Chem Biol. 2009 Sep;5(9):688-95
pubmed: 19648932
Structure. 2008 Jun;16(6):897-905
pubmed: 18547522
J Biol Chem. 2011 Mar 25;286(12):9985-97
pubmed: 21247891
Mol Pharmacol. 2009 Mar;75(3):637-47
pubmed: 19047484
J Biol Chem. 2009 Jul 17;284(29):19533-43
pubmed: 19451648
Nature. 2020 Jul;583(7818):862-866
pubmed: 32555462
J Biol Chem. 2004 Apr 16;279(16):16091-100
pubmed: 14764600
Front Pharmacol. 2018 Aug 30;9:829
pubmed: 30214407
Nat Commun. 2021 Jun 24;12(1):3938
pubmed: 34168117
Cell. 2019 Jun 13;177(7):1933-1947.e25
pubmed: 31160049
Nature. 2020 Mar;579(7798):303-308
pubmed: 31945771
Cell Rep. 2016 Jan 12;14(2):390-400
pubmed: 26748717
Cancer Res. 2015 Oct 1;75(19):4198-210
pubmed: 26359459
Nat Chem Biol. 2010 Aug;6(8):587-94
pubmed: 20622858
Nature. 2021 Jun;594(7864):583-588
pubmed: 34135510
Cell. 2017 Jul 27;170(3):457-469.e13
pubmed: 28753425
J Biol Chem. 2004 Nov 12;279(46):47438-45
pubmed: 15339913
J Immunol. 2006 Jun 1;176(11):7039-50
pubmed: 16709866
FASEB J. 2014 Oct;28(10):4509-23
pubmed: 25053617
Nat Struct Mol Biol. 2018 Jun;25(6):488-495
pubmed: 29808000
J Biol Chem. 2004 Aug 27;279(35):36179-83
pubmed: 15231824
J Biol Chem. 1997 Oct 24;272(43):26959-64
pubmed: 9341132
Proc Natl Acad Sci U S A. 2020 Sep 1;117(35):21711-21722
pubmed: 32817431
Sci Adv. 2021 Jun 9;7(24):
pubmed: 34108205
Cell Res. 2019 Dec;29(12):971-983
pubmed: 31776446
Nature. 1998 Dec 17;396(6712):679-82
pubmed: 9872316
Neuropharmacology. 2019 Jul 1;152:15-21
pubmed: 30419245
Nature. 2020 Mar;579(7798):297-302
pubmed: 31945772
Int J Cancer. 2005 Jan 20;113(3):503-5
pubmed: 15455343
Faraday Discuss. 2018 Apr 1;207:409-421
pubmed: 29359206
Nat Commun. 2016 Jul 11;7:12178
pubmed: 27397672
Nat Rev Drug Discov. 2017 Dec;16(12):829-842
pubmed: 29075003
Trends Pharmacol Sci. 2007 Aug;28(8):423-30
pubmed: 17659355
Nat Methods. 2019 Jun;16(6):493-496
pubmed: 31110281
Nat Methods. 2008 Jun;5(6):561-7
pubmed: 18488035
Nat Commun. 2016 Feb 24;7:10842
pubmed: 26905976
Fitoterapia. 2013 Jan;84:180-201
pubmed: 23160091
Cell. 2017 Jul 27;170(3):414-427
pubmed: 28753422
Biochem J. 1993 Jun 15;292 ( Pt 3):617-29
pubmed: 8391253
Sci Rep. 2016 Sep 12;6:33233
pubmed: 27615810
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24
pubmed: 20080658
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7682-7
pubmed: 17452637
Nat Chem Biol. 2016 Jan;12(1):35-9
pubmed: 26571351
Pharmacol Ther. 2019 Aug;200:148-178
pubmed: 31075355
Nat Rev Mol Cell Biol. 2018 Oct;19(10):638-653
pubmed: 30104700
Gut. 2004 Jun;53(6):877-83
pubmed: 15138217
Nat Chem Biol. 2020 Sep;16(9):946-954
pubmed: 32541966
Cell. 2020 Sep 3;182(5):1362-1362.e1
pubmed: 32888497
Nat Commun. 2018 Jan 23;9(1):341
pubmed: 29362459