PXD033733

PXD033733 is an original dataset announced via ProteomeXchange.

Title	Mapping of the autophagosomal degradome identifies IL-7Rα as key 1 cargo in proliferating CD4+ T-cells
Description	CD4+ T cells orchestrate both humoral and cytotoxic immune responses. While it is known that CD4+ T cell proliferation relies on autophagy, direct identification of the autophagosomal cargo involved is still missing. Here, we created a transgenic mouse model, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell by LC3 proximity labelling. IL-7Rα, a cytokine receptor mostly found in naïve and memory T cells, was reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy showed increased IL-7Rα surface expression, while no defect in internalisation was observed. Mechanistically, excessive surface IL-7Rα sequestrates the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. This study provides proof-of-principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy’s contribution to healthy physiology and disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:37.218.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-06 03:31:48	ID requested
1	2022-07-08 04:30:50	announced
⏵ 2	2023-11-14 08:56:38	announced	2023-11-14: Updated project metadata.

Zhou D, Borsa M, Puleston DJ, Zellner S, Capera J, Sanderson S, Schifferer M, Hester SS, Ge X, Fischer R, Jostins L, Behrends C, Alsaleh G, Simon AK, T cell proliferation. Nat Commun, 13(1):5174(2022) [pubmed]

submitter keyword: IL-7Ra autophagosome degradome

Roman Fischer
contact affiliation	Discovery Proteomics Facility, University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
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/2022/07/PXD033733

PRIDE project URI

• PRIDE
  1. PXD033733
     1. Label: PRIDE project
     2. Name: Mapping of the autophagosomal degradome identifies IL-7Rα as key 1 cargo in proliferating CD4+ T-cells