PXD018763

PXD018763 is an original dataset announced via ProteomeXchange.

Title	Clustering of Tir during E. coli infection affects Ca2+-dependent LPS internalisation leading to activation of pyroptosis in intestinal epithelial cells
Description	Clustering of the Enteropathogenic (EPEC) Escherichia coli Tir effector, induced by its binding to Intimin, leads to pyroptotic cell death in macrophages. The effect of Tir clustering following EPEC infection of epithelial cells remains unexplored. In this study, we show that EPEC induces pyroptosis in an intestinal epithelial cell (IEC) line, in a Tir-dependent but actin polymerisation-independent manner, which was enhanced by priming with IFNγ. Mechanistically, Tir clustering induces rapid Ca2+ influx, which promotes internalisation of LPS, followed by activation of caspase-4. Chelation of extracellular Ca2+ or knockdown of caspase-4 inhibited cell death upon EPEC infection, whereas ATP-induced extracellular Ca2+ influx had the opposite effect confirming the regulatory role of calcium in the pathway. Additionally, IEC lines with low endogenous expression of caspase-4 were resistant to EPEC-induced cell death. We reveal a novel mechanism of LPS internalisation, following infection with an extracellular pathogen, leading to pyroptosis in IECs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:14:19.379.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-23 05:27:56	ID requested
1	2020-10-28 06:39:52	announced
⏵ 2	2024-10-22 05:14:19	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: TMT, Human,E.coli, IEC, msms, cell line

Jyoti Choudhary
contact affiliation	The Institute of Cancer Research, London
contact email	Jyoti.choudhary@icr.ac.uk
lab head
James Wright
contact affiliation	The Institute of Cancer Research
contact email	james.wright@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018763
     1. Label: PRIDE project
     2. Name: Clustering of Tir during E. coli infection affects Ca2+-dependent LPS internalisation leading to activation of pyroptosis in intestinal epithelial cells