Ataxin-3 Links NOD2 and TLR2 Mediated Innate Immune Sensing and Metabolism in Myeloid Cells.
Ataxin-3
/ immunology
Cell Respiration
HEK293 Cells
Humans
Immunity, Innate
Mitochondria
/ metabolism
Myeloid Cells
/ immunology
Nod2 Signaling Adaptor Protein
/ immunology
Phosphorylation
Protein Serine-Threonine Kinases
/ immunology
Reactive Oxygen Species
/ metabolism
Receptor-Interacting Protein Serine-Threonine Kinase 2
/ immunology
Signal Transduction
THP-1 Cells
Toll-Like Receptor 2
/ immunology
Nod2
TLR2
ataxin 3
innate immnuity
metabolism
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2019
2019
Historique:
received:
02
04
2019
accepted:
14
06
2019
entrez:
6
8
2019
pubmed:
6
8
2019
medline:
23
10
2020
Statut:
epublish
Résumé
The interplay between NOD2 and TLR2 following recognition of components of the bacterial cell wall peptidoglycan is well-established, however their role in redirecting metabolic pathways in myeloid cells to degrade pathogens and mount antigen presentation remains unclear. We show NOD2 and TLR2 mediate phosphorylation of the deubiquitinase ataxin-3 via RIPK2 and TBK1. In myeloid cells ataxin-3 associates with the mitochondrial cristae protein MIC60, and is required for oxidative phosphorylation. Depletion of ataxin-3 leads to impaired induction of mitochondrial reactive oxygen species (mROS) and defective bacterial killing. A mass spectrometry analysis of NOD2/TLR2 triggered ataxin-3 deubiquitination targets revealed immunometabolic regulators, including HIF-1α and LAMTOR1 that may contribute to these effects. Thus, we define how ataxin-3 plays an essential role in NOD2 and TLR2 sensing and effector functions in myeloid cells.
Identifiants
pubmed: 31379806
doi: 10.3389/fimmu.2019.01495
pmc: PMC6659470
doi:
Substances chimiques
NOD2 protein, human
0
Nod2 Signaling Adaptor Protein
0
Reactive Oxygen Species
0
TLR2 protein, human
0
Toll-Like Receptor 2
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
RIPK2 protein, human
EC 2.7.11.1
Receptor-Interacting Protein Serine-Threonine Kinase 2
EC 2.7.11.1
TBK1 protein, human
EC 2.7.11.1
Ataxin-3
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1495Subventions
Organisme : Department of Health
ID : NIHR-RP-R3-12-026
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/7
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0501068
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/7
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S036377/1
Pays : United Kingdom
Références
Immunity. 1999 Jan;10(1):29-38
pubmed: 10023768
Nature. 2001 May 31;411(6837):599-603
pubmed: 11385576
Nature. 2001 May 31;411(6837):603-6
pubmed: 11385577
Nature. 2002 Mar 14;416(6877):194-9
pubmed: 11894098
J Biol Chem. 2002 Nov 22;277(47):45004-12
pubmed: 12297501
J Biol Chem. 2003 Mar 14;278(11):8869-72
pubmed: 12527755
Cell. 2003 Mar 7;112(5):645-57
pubmed: 12628185
Cell Cycle. 2003 May-Jun;2(3):192-3
pubmed: 12734422
Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4330-5
pubmed: 15767577
J Immunol. 2005 May 15;174(10):6518-23
pubmed: 15879155
Lancet. 2005 May 21-27;365(9473):1794-6
pubmed: 15910952
J Clin Invest. 2005 Jul;115(7):1806-15
pubmed: 16007254
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10493-8
pubmed: 16020535
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12700-5
pubmed: 16118278
Hum Mol Genet. 2006 Aug 15;15(16):2409-20
pubmed: 16822850
J Immunol. 2007 Jun 15;178(12):7516-9
pubmed: 17548584
J Neurosci. 2007 Jul 4;27(27):7310-7
pubmed: 17611283
EMBO J. 2008 Jan 23;27(2):373-83
pubmed: 18079694
Drug Discov Today. 2008 Mar;13(5-6):268-74
pubmed: 18342804
J Biol Chem. 2008 Sep 26;283(39):26436-43
pubmed: 18599482
Biochem J. 2009 Jan 1;417(1):1-13
pubmed: 19061483
EMBO J. 2009 Mar 4;28(5):477-89
pubmed: 19177150
Biopolymers. 2009 Dec;91(12):1203-14
pubmed: 19382171
Annu Rev Biochem. 2009;78:363-97
pubmed: 19489724
EMBO Rep. 2009 Nov;10(11):1250-8
pubmed: 19798103
Genome Biol. 2009;10(11):R130
pubmed: 19919682
Nat Med. 2010 Jan;16(1):90-7
pubmed: 19966812
Cell. 2010 Mar 19;140(6):805-20
pubmed: 20303872
Blood. 2010 Jun 10;115(23):4742-9
pubmed: 20351312
Cell. 2010 Apr 16;141(2):290-303
pubmed: 20381137
PLoS One. 2010 Jun 08;5(6):e10977
pubmed: 20544018
Nature. 2011 Apr 28;472(7344):476-80
pubmed: 21525932
J Inherit Metab Dis. 2011 Aug;34(4):941-51
pubmed: 21541724
Science. 2011 Jul 8;333(6039):228-33
pubmed: 21617041
Handb Clin Neurol. 2012;103:437-49
pubmed: 21827905
Mol Cell. 2011 Oct 21;44(2):325-40
pubmed: 21906983
Dev Cell. 2011 Oct 18;21(4):694-707
pubmed: 21944719
EMBO J. 2011 Oct 18;30(21):4356-70
pubmed: 22009199
Science. 2011 Nov 4;334(6056):678-83
pubmed: 22053050
Immunity. 2012 Jan 27;36(1):68-78
pubmed: 22206904
Biochem Biophys Res Commun. 2012 Jan 27;417(4):1151-7
pubmed: 22227194
Protein Cell. 2012 Sep;3(9):675-90
pubmed: 22802047
Mol Biol Cell. 2012 Oct;23(20):3948-56
pubmed: 22918945
Cell. 2012 Sep 14;150(6):1196-208
pubmed: 22980980
Immunity. 2013 Sep 19;39(3):521-36
pubmed: 24054330
Mol Neurobiol. 2014 Jun;49(3):1513-31
pubmed: 24293103
Nat Rev Immunol. 2014 Jan;14(1):9-23
pubmed: 24336102
Nature. 2014 Jan 23;505(7484):550-554
pubmed: 24336208
Gut Microbes. 2014 May-Jun;5(3):340-4
pubmed: 24637801
Nat Rev Immunol. 2014 Jul;14(7):463-77
pubmed: 24962261
Cell Metab. 2014 Sep 2;20(3):526-40
pubmed: 25002183
Front Immunol. 2014 Jul 10;5:317
pubmed: 25071778
Nat Immunol. 2014 Sep;15(9):846-55
pubmed: 25086775
Front Immunol. 2014 Sep 25;5:461
pubmed: 25309543
Immunity. 2014 Oct 16;41(4):518-28
pubmed: 25367569
Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20
pubmed: 25514926
PLoS Genet. 2015 Jan 15;11(1):e1004834
pubmed: 25590633
Sci Rep. 2015 Jan 23;5:7990
pubmed: 25612828
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
PLoS Genet. 2015 Jan 29;11(1):e1004749
pubmed: 25633985
Osteoarthritis Cartilage. 2015 Sep;23(9):1575-85
pubmed: 25917637
Hum Mol Genet. 2015 Aug 1;24(15):4429-42
pubmed: 25972374
Cell Death Differ. 2016 Mar;23(3):380-92
pubmed: 26250910
Chem Biol. 2015 Sep 17;22(9):1174-84
pubmed: 26320862
J Exp Med. 2016 Jan 11;213(1):15-23
pubmed: 26694970
Nat Rev Immunol. 2016 Jan;16(1):35-50
pubmed: 26711677
Sci Rep. 2016 Feb 02;6:20295
pubmed: 26830977
Cell Res. 2016 Apr;26(4):399-422
pubmed: 27012465
Cell Res. 2016 Apr;26(4):457-83
pubmed: 27012466
Nat Immunol. 2016 Sep;17(9):1037-1045
pubmed: 27348412
Nat Rev Immunol. 2016 Sep;16(9):553-65
pubmed: 27396447
Methods Mol Biol. 2016;1449:161-75
pubmed: 27613034
Methods Mol Biol. 2016;1449:177-92
pubmed: 27613035
Semin Immunol. 2016 Oct;28(5):469-477
pubmed: 27717536
Nat Commun. 2016 Oct 12;7:13130
pubmed: 27731330
J Proteome Res. 2017 Mar 3;16(3):1288-1299
pubmed: 28164708
Nature. 2017 May 4;545(7652):108-111
pubmed: 28445460
Brain. 2017 Nov 1;140(11):2860-2878
pubmed: 29053796
Mol Immunol. 2017 Nov 29;:null
pubmed: 29198621
Front Med (Lausanne). 2018 Feb 19;5:32
pubmed: 29515999
J Immunol. 2018 Jul 15;201(2):675-687
pubmed: 29802126
Nat Immunol. 2018 Sep;19(9):942-953
pubmed: 30111894
Nat Genet. 1994 Nov;8(3):221-8
pubmed: 7874163