Cells Responding to Closely Related Cholesterol-Dependent Cytolysins Release Extracellular Vesicles with a Common Proteomic Content Including Membrane Repair Proteins.
calcium influx
extracellular vesicles
listeriolysin O
plasma membrane repair
pneumolysin
pore-forming toxins
proteomics
shedding
Journal
Toxins
ISSN: 2072-6651
Titre abrégé: Toxins (Basel)
Pays: Switzerland
ID NLM: 101530765
Informations de publication
Date de publication:
20 12 2022
20 12 2022
Historique:
received:
10
11
2022
revised:
15
12
2022
accepted:
16
12
2022
entrez:
20
1
2023
pubmed:
21
1
2023
medline:
25
1
2023
Statut:
epublish
Résumé
The plasma membrane (PM) protects cells from extracellular threats and supports cellular homeostasis. Some pathogens produce pore-forming toxins (PFTs) that disrupt PM integrity by forming transmembrane pores. High PFT concentrations cause massive damage leading to cell death and facilitating infection. Sub-lytic PFT doses activate repair mechanisms to restore PM integrity, support cell survival and limit disease. Shedding of extracellular vesicles (EVs) has been proposed as a key mechanism to eliminate PFT pores and restore PM integrity. We show here that cholesterol-dependent cytolysins (CDCs), a specific family of PFTs, are at least partially eliminated through EVs release, and we hypothesize that proteins important for PM repair might be included in EVs shed by cells during repair. To identify new PM repair proteins, we collected EVs released by cells challenged with sub-lytic doses of two different bacterial CDCs, listeriolysin O and pneumolysin, and determined the EV proteomic repertoire by LC-MS/MS. Intoxicated cells release similar EVs irrespectively of the CDC used. Also, they release more and larger EVs than non-intoxicated cells. A cluster of 70 proteins including calcium-binding proteins, molecular chaperones, cytoskeletal, scaffold and membrane trafficking proteins, was detected enriched in EVs collected from intoxicated cells. While some of these proteins have well-characterized roles in repair, the involvement of others requires further study. As proof of concept, we show here that Copine-1 and Copine-3, proteins abundantly detected in EVs released by intoxicated cells, are required for efficient repair of CDC-induced PM damage. Additionally, we reveal here new proteins potentially involved in PM repair and give new insights into common mechanisms and machinery engaged by cells in response to PM damage.
Identifiants
pubmed: 36668824
pii: toxins15010004
doi: 10.3390/toxins15010004
pmc: PMC9865450
pii:
doi:
Substances chimiques
Cytotoxins
0
Membrane Proteins
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Références
J Cell Sci. 2011 Jul 15;124(Pt 14):2414-23
pubmed: 21693578
Commun Integr Biol. 2012 Jul 1;5(4):308-11
pubmed: 23060949
J Leukoc Biol. 2003 Sep;74(3):379-88
pubmed: 12949241
Traffic. 2007 Jun;8(6):742-57
pubmed: 17488290
Curr Top Membr. 2019;84:43-65
pubmed: 31610865
EMBO J. 2021 Apr 1;40(7):e106922
pubmed: 33644904
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
EMBO Rep. 2017 Feb;18(2):303-318
pubmed: 28039206
PLoS One. 2014 Jan 10;9(1):e85438
pubmed: 24427308
Cell Host Microbe. 2011 Feb 17;9(2):147-57
pubmed: 21320697
Commun Integr Biol. 2017 Sep 28;10(5-6):e1349582
pubmed: 29259728
Cell Death Differ. 2017 May;24(5):798-808
pubmed: 28186501
JCI Insight. 2022 Jul 22;7(14):
pubmed: 35866481
Front Immunol. 2022 Apr 22;13:878244
pubmed: 35529870
Protein Sci. 2022 Jan;31(1):8-22
pubmed: 34717010
Cell Discov. 2021 Jan 19;7(1):4
pubmed: 33462191
FASEB J. 2020 Jan;34(1):1665-1678
pubmed: 31914676
Nat Cell Biol. 2002 Dec;4(12):955-62
pubmed: 12447386
Sci Rep. 2018 Jul 17;8(1):10813
pubmed: 30018314
Microbiology (Reading). 2022 Mar;168(3):
pubmed: 35333704
J Proteome Res. 2013 Jul 5;12(7):3423-33
pubmed: 23713811
J Biol Chem. 2011 Nov 18;286(46):40174-83
pubmed: 21949189
Sci Rep. 2021 May 5;11(1):9529
pubmed: 33953279
Biochimie. 2014 Dec;107 Pt A:66-72
pubmed: 25183513
Sci Rep. 2021 Feb 19;11(1):4226
pubmed: 33608587
Microbiol Mol Biol Rev. 2013 Jun;77(2):173-207
pubmed: 23699254
Sci Rep. 2018 Oct 26;8(1):15846
pubmed: 30367146
Cell Host Microbe. 2008 Aug 14;4(2):100-9
pubmed: 18692770
J Neuroinflammation. 2018 May 28;15(1):168
pubmed: 29807527
Biochim Biophys Acta. 2015 Sep;1853(9):2045-54
pubmed: 25219550
Science. 2014 Feb 28;343(6174):1247136
pubmed: 24482116
J Biol Chem. 1998 Jan 16;273(3):1393-402
pubmed: 9430674
FEMS Microbiol Lett. 2000 Jan 15;182(2):197-205
pubmed: 10620666
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4341-6
pubmed: 20145114
FASEB J. 2004 May;18(7):839-41
pubmed: 15001564
Nat Rev Microbiol. 2016 Feb;14(2):77-92
pubmed: 26639780
Front Genet. 2021 Jul 23;12:689097
pubmed: 34367247
Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
pubmed: 18228490
Biochem Cell Biol. 2006 Aug;84(4):589-604
pubmed: 16936831
Cell Mol Life Sci. 2019 Apr;76(7):1319-1339
pubmed: 30591958
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Front Immunol. 2018 Jul 27;9:1688
pubmed: 30100903
Annu Rev Immunol. 2020 Apr 26;38:455-485
pubmed: 32004099
Infect Immun. 1991 Dec;59(12):4641-6
pubmed: 1937824
Cell Death Differ. 2009 Aug;16(8):1126-34
pubmed: 19325569
Cell Death Differ. 2011 Jan;18(1):80-9
pubmed: 20596076
Oncogene. 2008 Jun 5;27(25):3516-26
pubmed: 18212740
FASEB J. 2019 Jan;33(1):275-285
pubmed: 29979630
PLoS One. 2014 Feb 21;9(2):e89743
pubmed: 24587004
Toxins (Basel). 2019 Jul 17;11(7):
pubmed: 31319618
Front Cell Infect Microbiol. 2017 Jul 14;7:305
pubmed: 28770170
Methods Mol Biol. 2009;563:123-40
pubmed: 19597783
BMC Cell Biol. 2018 Jul 16;19(1):13
pubmed: 30012091
Toxins (Basel). 2013 Apr 12;5(4):618-36
pubmed: 23584137
Biochim Biophys Acta. 2016 Nov;1860(11 Pt A):2498-2509
pubmed: 27481675
Nat Methods. 2014 Aug;11(8):783-784
pubmed: 25075903
Cell. 2022 Aug 18;185(17):3201-3213.e19
pubmed: 35985289
J Biol Chem. 2021 Jan-Jun;296:100182
pubmed: 33310703
Chem Rev. 2019 Jul 10;119(13):7721-7736
pubmed: 31244002
Mol Cell. 2017 Jun 15;66(6):780-788
pubmed: 28622523
J Cell Biol. 2004 Jan 5;164(1):133-44
pubmed: 14699089
J Cell Biol. 2002 Mar 18;156(6):1029-38
pubmed: 11901168
Nat Protoc. 2019 Jan;14(1):68-85
pubmed: 30464214
Sci Rep. 2020 Dec 11;10(1):21821
pubmed: 33311633
Blood Rev. 2013 Jan;27(1):31-9
pubmed: 23261067
Biophys Rev. 2018 Oct;10(5):1337-1348
pubmed: 30117093
Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13467-72
pubmed: 17675409