PXD037799

PXD037799 is an original dataset announced via ProteomeXchange.

Title	CD44 acts as a co-receptor to confer cell type-specific enhancement of signaling and regulatory T cell induction by TGM-1, a helminth parasite mimic of TGF
Description	Long-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, Heligmosomoides polygyrus, suppresses the host immune system through release of an immunoregulatory TGF-β mimic, TGM-1, which is a divergent member of the CCP (Sushi) protein family. TGM-1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGFβ receptors, acting on T cells to induce Foxp3+ regulatory T cells; however, the roles of domains 4 and 5 (D4-5) remain unknown. We noted that a truncated TGM-1, lacking these domains, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not restore full potency, suggesting that a physical linkage is required, and that these domains may not deliver an independent signal. Co-precipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a co-receptor for TGM-1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, while D1/2/3 binding was only marginally detectable. Ectopic expression of CD44 in non responding cells conferred responsiveness, while specific genetic depletion of CD44 abolished the enhancement effect of D4/5, and ablated the ability of full-length TGM-1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM-1, to levels similar to D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type-specific potency of TGF-β signaling in mammalian cells.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:17.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Román González-Prieto
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-28 07:20:14	ID requested
1	2023-10-24 07:13:48	announced
⏵ 2	2023-11-14 09:06:19	announced	2023-11-14: Updated project metadata.

van Dinther M, Cunningham KT, Singh SP, White MPJ, Campion T, Ciancia C, van Veelen PA, de Ru AH, Gonz, á, lez-Prieto R, Mukundan A, Byeon CH, Staggers SR, Hinck CS, Hinck AP, Dijke PT, Maizels RM, mimic. Proc Natl Acad Sci U S A, 120(34):e2302370120(2023) [pubmed]

submitter keyword: Heligmosomoides polygyrus, TGF- mimic, Lymphocyte, Convergent evolution, Fibroblast,Complement Control Protein

Román González-Prieto
contact affiliation	Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER) - University of Seville
contact email	roman.gonzalez@cabimer.es
lab head
Román González-Prieto
contact affiliation	Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact email	roman.gonzalez@cabimer.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD037799

PRIDE project URI

• PRIDE
  1. PXD037799
     1. Label: PRIDE project
     2. Name: CD44 acts as a co-receptor to confer cell type-specific enhancement of signaling and regulatory T cell induction by TGM-1, a helminth parasite mimic of TGF