Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
31 03 2023
31 03 2023
Historique:
medline:
3
4
2023
entrez:
30
3
2023
pubmed:
31
3
2023
Statut:
ppublish
Résumé
Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology. Tau-Ab complexes were internalized to the cytosol of neurons, which enabled T21 engagement and protection against seeded aggregation. Ab-mediated protection against tau pathology was lost in mice that lacked T21. Thus, the cytosolic compartment provides a site of immunotherapeutic protection, which may help in the design of Ab-based therapies in neurodegenerative disease.
Identifiants
pubmed: 36996217
doi: 10.1126/science.abn1366
pmc: PMC7614512
mid: EMS174787
doi:
Substances chimiques
Antibodies, Monoclonal
0
Receptors, Fc
0
Ribonucleoproteins
0
SS-A antigen
0
tau Proteins
0
Tripartite Motif Proteins
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1336-1341Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206248
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105181010
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105184291
Pays : United Kingdom
Références
J Biol Chem. 2013 Dec 6;288(49):35452-65
pubmed: 24163366
FEBS Lett. 2018 Jul;592(14):2383-2391
pubmed: 29790176
Brain. 2014 Oct;137(Pt 10):2834-46
pubmed: 25085375
Neuron. 1992 Jan;8(1):159-68
pubmed: 1530909
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
EMBO J. 1990 Dec;9(13):4225-30
pubmed: 2124967
Nat Med. 2018 Feb;24(2):186-193
pubmed: 29334375
Acta Neuropathol Commun. 2019 Mar 18;7(1):44
pubmed: 30885267
Cell Rep. 2022 May 3;39(5):110776
pubmed: 35508140
Sci Rep. 2019 Mar 15;9(1):4658
pubmed: 30874605
Nat Protoc. 2012 Sep;7(9):1741-54
pubmed: 22936216
Curr Protoc Cell Biol. 2018 Jun;79(1):e51
pubmed: 29924488
J Exp Med. 2016 Nov 14;213(12):2635-2654
pubmed: 27810929
J Immunol Methods. 1997 May 12;204(1):77-87
pubmed: 9202712
PLoS One. 2011;6(12):e26860
pubmed: 22174735
Cell Rep. 2018 Mar 27;22(13):3612-3624
pubmed: 29590627
Nat Immunol. 2013 Apr;14(4):327-36
pubmed: 23455675
J Biol Chem. 2013 Nov 15;288(46):33081-95
pubmed: 24089520
Front Immunol. 2019 May 31;10:1139
pubmed: 31214163
Brain. 2019 Jun 1;142(6):1736-1750
pubmed: 31038156
Nature. 2015 Jul 23;523(7561):431-436
pubmed: 26176913
Nat Cell Biol. 2009 Jul;11(7):909-13
pubmed: 19503072
Cell Rep. 2016 Aug 9;16(6):1690-1700
pubmed: 27475227
Cell. 2017 Dec 14;171(7):1692-1706.e18
pubmed: 29153837
J Neurosci. 2002 Nov 1;22(21):9340-51
pubmed: 12417659
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6200-5
pubmed: 17400754
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10440-10445
pubmed: 30209217
Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):10014-9
pubmed: 26150489
J Immunol. 2016 Apr 15;196(8):3452-3459
pubmed: 26962230
J Biol Chem. 2021 Jan-Jun;296:100715
pubmed: 33930462
FEBS Lett. 1996 Apr 8;384(1):25-30
pubmed: 8797796
J Biol Chem. 2017 Mar 3;292(9):3900-3908
pubmed: 28077575
J Biol Chem. 2011 Sep 30;286(39):34457-67
pubmed: 21841002
J Neurosci. 2007 Aug 22;27(34):9115-29
pubmed: 17715348
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):E3138-47
pubmed: 23898162
J Immunol. 2009 Jun 15;182(12):7527-38
pubmed: 19494276
Sci Rep. 2018 Apr 23;8(1):6382
pubmed: 29686391
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19985-90
pubmed: 21045130
Sci Rep. 2021 Jun 30;11(1):13602
pubmed: 34193922
Neuron. 1989 Oct;3(4):519-26
pubmed: 2484340
J Biol Chem. 2015 Aug 28;290(35):21652-62
pubmed: 26126828
Acta Neuropathol Commun. 2021 Mar 12;9(1):41
pubmed: 33712082
Sci Rep. 2015 Jun 09;5:11161
pubmed: 26057852
Nature. 2020 Apr;580(7803):381-385
pubmed: 32296178
Elife. 2018 Jul 10;7:
pubmed: 29988016
J Virol. 2012 Aug;86(16):8482-91
pubmed: 22647693
Nat Struct Mol Biol. 2021 Mar;28(3):278-289
pubmed: 33633400
Neuron. 2013 Oct 16;80(2):402-414
pubmed: 24075978
Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):574-579
pubmed: 28049840