PXD025055-1

PXD025055 is an original dataset announced via ProteomeXchange.

Title	Identification of a novel class of cytotoxic granules as origin of supramolecular attack particles in T lymphocytes
Description	Cytotoxic T lymphocytes (CTL) kill malignant and infected cells via cytotoxic proteins such as granzyme B (GzmB) that are released into the immunological synapse in the form of ~110 nm supramolecular attack particles (SMAPs). However, it is not known where SMAPs are stored in the cell and how they are released. To address this, we utilized knock-in mice to label fusogenic cytotoxic granules with synaptobrevin2-mRFP. We identified two classes of fusion-competent granules, single core granules (SCG) and multi core granules (MCG), with different diameter, morphology, and protein composition. Functional analyses demonstrate that both classes of granules fuse with the plasma membrane at the IS. SCG fusion resulted in rapid dispersal of GzmB. MCG labelled with the SMAP marker thrombospondin-1 and their fusion events resulted in deposition of SMAPs. The CTL attack strategy thus includes SCG fusion to disperse immediately active cytotoxic proteins and parallel MCG fusion to deposit concentrated latent SMAPs onto the target.
HostingRepository	PRIDE
AnnounceDate	2022-04-06
AnnouncementXML	Submission_2022-04-06_09:19:31.220.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Momchil Ninov
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-29 02:45:12	ID requested
⏵ 1	2022-04-06 09:19:32	announced

Chang HF, Schirra C, Ninov M, Hahn U, Ravichandran K, Krause E, Becherer U, B, á, lint Š, Harkiolaki M, Urlaub H, Valitutti S, Baldari CT, Dustin ML, Jahn R, Rettig J, Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes. Nat Commun, 13(1):1029(2022) [pubmed]

submitter keyword: SNARE proteins, exocytosis, cytotoxic granules, immunological synapse, proteomics, single core granules, multi core granules, supramolecular attack particles, total internal reflection fluorescence microscopy, correlative light and electron microscopy

Henning Urlaub
contact affiliation	Prof. Dr. Henning Urlaub Max-Planck-Institute for Biophysical Chemistry Bioanalytical Mass Spectrometry Group Am Fassberg 11 D-37077 Goettingen, Germany University Medical Center Goettingen Bioanalytics Institute for Clinical Chemistry Robert Koch Strasse 40 D-37075 Goettingen, Germany
contact email	henning.urlaub@mpibpc.mpg.de
lab head
Momchil Ninov
contact affiliation	Max Planck Institute for Biophysical Chemistry, Bioanalytical Mass Spectrometry - Göttingen, Germany University Medical Center, Institute for Clinical Chemistry, Bioanalytics Group - Göttingen, Germany
contact email	momchil.ninov@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025055
     1. Label: PRIDE project
     2. Name: Identification of a novel class of cytotoxic granules as origin of supramolecular attack particles in T lymphocytes