Deficiency in coatomer complex I causes aberrant activation of STING signalling.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 04 2022
28 04 2022
Historique:
received:
17
07
2020
accepted:
05
04
2022
entrez:
28
4
2022
pubmed:
29
4
2022
medline:
3
5
2022
Statut:
epublish
Résumé
Coatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within Golgi compartments. Deficiency in subunit alpha causes COPA syndrome and is associated with type I IFN signalling, although the upstream innate immune sensor involved was unknown. Using in vitro models we find aberrant activation of the STING pathway due to deficient retrograde but probably not intra-Golgi transport. Further we find the upstream cytosolic DNA sensor cGAS as essentially required to drive type I IFN signalling. Genetic deletion of COPI subunits COPG1 or COPD similarly induces type I IFN activation in vitro, which suggests that inflammatory diseases associated with mutations in other COPI subunit genes may exist. Finally, we demonstrate that inflammation in COPA syndrome patient peripheral blood mononuclear cells and COPI-deficient cell lines is ameliorated by treatment with the small molecule STING inhibitor H-151, suggesting targeted inhibition of the cGAS/STING pathway as a promising therapeutic approach.
Identifiants
pubmed: 35484149
doi: 10.1038/s41467-022-29946-6
pii: 10.1038/s41467-022-29946-6
pmc: PMC9051092
doi:
Substances chimiques
Coat Protein Complex I
0
Nucleotidyltransferases
EC 2.7.7.-
Electron Transport Complex I
EC 7.1.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2321Subventions
Organisme : Wellcome Trust
ID : 208694/Z/17/Z
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Science. 2014 Jan 3;343(6166):84-87
pubmed: 24336571
Trends Cell Biol. 2020 Aug;30(8):594-605
pubmed: 32546434
EMBO J. 2014 Dec 17;33(24):2937-46
pubmed: 25425575
Cell Rep. 2017 Dec 12;21(11):3234-3242
pubmed: 29241549
J Biol Chem. 2018 Sep 28;293(39):15195-15207
pubmed: 30076215
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8653-8
pubmed: 19433799
Cell Rep. 2015 Mar 3;10(8):1422-32
pubmed: 25732831
Nat Immunol. 2020 Aug;21(8):868-879
pubmed: 32690950
Viruses. 2020 Jan 24;12(2):
pubmed: 31991682
Cell. 2019 Jul 11;178(2):290-301.e10
pubmed: 31230712
Eur J Rheumatol. 2019 Aug 20;:1-4
pubmed: 31449490
Immunity. 2008 Oct 17;29(4):538-50
pubmed: 18818105
Sci Rep. 2017 Oct 20;7(1):13683
pubmed: 29057981
Cell. 1989 Mar 10;56(5):801-13
pubmed: 2647301
J Biochem. 2000 Nov;128(5):793-801
pubmed: 11056392
J Biol Chem. 1990 May 5;265(13):7248-56
pubmed: 2332429
J Neuroinflammation. 2015 Oct 31;12:199
pubmed: 26520095
J Immunol. 2019 Sep 15;203(6):1560-1570
pubmed: 31391232
Cell. 1987 Mar 13;48(5):899-907
pubmed: 3545499
Physiology (Bethesda). 2011 Oct;26(5):348-64
pubmed: 22013193
Arthritis Rheumatol. 2021 Nov;73(11):2105-2115
pubmed: 33982886
Mol Cell Biol. 2004 Feb;24(3):1070-80
pubmed: 14729954
J Med Genet. 2019 Nov;56(11):778-782
pubmed: 30385646
Cell Host Microbe. 2015 Aug 12;18(2):157-68
pubmed: 26235147
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4425-30
pubmed: 17360540
Life Sci Alliance. 2020 Jul 13;3(9):
pubmed: 32661021
Nat Genet. 2015 Jun;47(6):654-60
pubmed: 25894502
Cold Spring Harb Perspect Biol. 2011 Nov 01;3(11):a005231
pubmed: 21844168
J Exp Med. 2018 May 7;215(5):1287-1299
pubmed: 29622565
Cold Spring Harb Perspect Biol. 2011 Sep 01;3(9):a004424
pubmed: 21813400
Cell. 2014 Dec 18;159(7):1549-62
pubmed: 25525874
Genomics. 2010 Apr;95(4):210-6
pubmed: 20153416
Nature. 2013 Jun 20;498(7454):380-4
pubmed: 23722158
N Engl J Med. 2014 Aug 7;371(6):507-518
pubmed: 25029335
Mol Cell Biol. 2003 Nov;23(21):7448-59
pubmed: 14559994
Nat Commun. 2021 Jan 4;12(1):61
pubmed: 33397928
Science. 2015 Mar 13;347(6227):aaa2630
pubmed: 25636800
Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20842-6
pubmed: 19926846
Life Sci Alliance. 2020 Jul 14;3(9):
pubmed: 32665377
J Inflamm (Lond). 2017 Jun 7;14:11
pubmed: 28596706
Clin Immunol. 2018 Feb;187:33-36
pubmed: 29030294
Int J Biochem Cell Biol. 2012 Jan;44(1):16-20
pubmed: 22064245
Methods Mol Biol. 2017;1656:167-174
pubmed: 28808969
Cell Rep. 2018 Dec 11;25(11):3086-3098.e3
pubmed: 30540941
Int J Physiol Pathophysiol Pharmacol. 2016 Apr 25;8(1):35-43
pubmed: 27186321
EMBO J. 2000 Aug 1;19(15):3905-17
pubmed: 10921873
J Interferon Cytokine Res. 2006 Jun;26(6):373-9
pubmed: 16734557
Cell. 2014 Dec 18;159(7):1563-77
pubmed: 25525875
J Proteome Res. 2011 Apr 1;10(4):1794-805
pubmed: 21254760
Nature. 2019 Mar;567(7747):262-266
pubmed: 30842662
J Biol Chem. 2013 Jun 14;288(24):17908-17
pubmed: 23661706
Joint Bone Spine. 2021 Mar;88(2):105070
pubmed: 32919065
J Allergy Clin Immunol. 2017 Aug;140(2):543-552.e5
pubmed: 28087229
Science. 2016 Apr 15;352(6283):359-62
pubmed: 27013426
Hum Mol Genet. 2017 Dec 15;26(24):4836-4848
pubmed: 29036432
Nucleic Acids Res. 2016 Jun 20;44(11):5356-64
pubmed: 27166376
J Vasc Res. 2007;44(1):51-60
pubmed: 17167270
Nat Immunol. 2016 Jul;17(7):816-24
pubmed: 27213690
Methods Mol Biol. 2018;1784:35-49
pubmed: 29761386
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Am J Hum Genet. 2016 Aug 4;99(2):451-9
pubmed: 27476655
Nat Methods. 2014 Aug;11(8):783-784
pubmed: 25075903
Nature. 2009 Oct 8;461(7265):788-92
pubmed: 19776740
Immunity. 2018 May 15;48(5):911-922.e7
pubmed: 29768176
J Proteome Res. 2020 Jan 3;19(1):204-211
pubmed: 31657565
Science. 2013 Feb 15;339(6121):786-91
pubmed: 23258413
Science. 2013 Feb 15;339(6121):826-30
pubmed: 23258412
J Interferon Cytokine Res. 1998 Aug;18(8):549-54
pubmed: 9726434
Science. 2009 Jul 24;325(5939):477-81
pubmed: 19556461
FEBS Lett. 2009 Sep 3;583(17):2701-9
pubmed: 19631211
J Allergy Clin Immunol Pract. 2021 Feb;9(2):999-1001.e1
pubmed: 33099043
PLoS Biol. 2009 Sep;7(9):e1000194
pubmed: 19753100
Cell Rep. 2019 Jan 2;26(1):250-265.e5
pubmed: 30605680
J Exp Med. 2020 Nov 2;217(11):
pubmed: 32725126
Hum Mol Genet. 1999 Dec;8(13):2387-96
pubmed: 10556286
Biochem Biophys Res Commun. 2018 Sep 3;503(1):138-145
pubmed: 29870684
Cell Physiol Biochem. 2018;51(1):173-185
pubmed: 30439714
J Exp Med. 2020 Nov 2;217(11):
pubmed: 32725128
Science. 2015 Oct 30;350(6260):568-71
pubmed: 26405230
Nat Methods. 2009 May;6(5):359-62
pubmed: 19377485
Sci Signal. 2012 Mar 06;5(214):ra20
pubmed: 22394562
Elife. 2017 Feb 14;6:
pubmed: 28195529
Cell Rep. 2020 Apr 7;31(1):107492
pubmed: 32268090
Science. 2018 Aug 17;361(6403):704-709
pubmed: 29976794
BMC Med Genet. 2017 Nov 14;18(1):129
pubmed: 29137621
J Clin Invest. 2002 Nov;110(10):1383-8
pubmed: 12438433
EMBO J. 1998 Feb 16;17(4):985-95
pubmed: 9463377
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8642-7
pubmed: 9671731
Methods Mol Biol. 2018;1714:41-55
pubmed: 29177854
Nat Immunol. 2003 Jan;4(1):69-77
pubmed: 12483210
Mol Cell Biol. 2008 Aug;28(16):5014-26
pubmed: 18559423
J Clin Invest. 2021 Feb 1;131(3):
pubmed: 33529166
Thorax. 2020 Jan;75(1):92-95
pubmed: 31666386
J Cell Biol. 2009 Apr 20;185(2):305-21
pubmed: 19364919
Biochem J. 2011 Apr 1;435(1):285-96
pubmed: 21241252
Nat Rev Immunol. 2008 Sep;8(9):663-74
pubmed: 18670423
J Neuroimmunol. 2004 Nov;156(1-2):195-203
pubmed: 15465611
Sci Signal. 2017 Jan 03;10(460):
pubmed: 28049762
Cell Death Differ. 2019 Sep;26(9):1735-1749
pubmed: 30568238
Sci Signal. 2019 Aug 27;12(596):
pubmed: 31455725