Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes
2022 | journal article; research paper. A publication with affiliation to the University of Göttingen.
Jump to:Cite & Linked | Documents & Media | Details | Version history
Cite this publication
Chang, Hsin-Fang, Schirra, C., Ninov, M., Hahn, U., Ravichandran, K., Krause, E., Becherer, U. ... Rettig, J. (2022). Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes. Nature Communications, 13(1), Article 1029. doi: https://doi.org/10.1038/s41467-022-28596-y
Documents & Media
s41467-022-28596-y.pdf4.07 MBAdobe PDF41467_2022_28596_MOESM1_ESM.pdf3.69 MBAdobe PDF41467_2022_28596_MOESM2_ESM.pdf530.36 kBAdobe PDF41467_2022_28596_MOESM3_ESM.pdf81.69 kBAdobe PDF41467_2022_28596_MOESM4_ESM.xlsx563.84 kBMicrosoft Excel XML41467_2022_28596_MOESM9_ESM.pdf307.82 kBAdobe PDF41467_2022_28596_MOESM10_ESM.xlsx3.16 MBMicrosoft Excel XML
Details
- Authors
- Chang, Hsin-Fang; Schirra, Claudia; Ninov, Momchil; Hahn, Ulrike; Ravichandran, Keerthana; Krause, Elmar; Becherer, Ute; Bálint, Štefan; Harkiolaki, Maria; Urlaub, Henning ; Rettig, Jens
- Abstract
- Abstract Cytotoxic T lymphocytes (CTL) kill malignant and infected cells through the directed release of cytotoxic proteins into the immunological synapse (IS). The cytotoxic protein granzyme B (GzmB) is released in its soluble form or in supramolecular attack particles (SMAP). We utilize synaptobrevin2-mRFP knock-in mice to isolate fusogenic cytotoxic granules in an unbiased manner and visualize them alone or in degranulating CTLs. 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 releases soluble GzmB. MCGs can be labelled with the SMAP marker thrombospondin-1 and their fusion releases intact SMAPs. We propose that CTLs use SCG fusion to fill the synaptic cleft with active cytotoxic proteins instantly and parallel MCG fusion to deliver latent SMAPs for delayed killing of refractory targets.
- Issue Date
- 2022
- Journal
- Nature Communications
- Project
- SFB 1286: Quantitative Synaptologie
SFB 1286 | A08: Die Rolle post-translational modifizierter Proteine in der synaptischen Übertragung
SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen - Working Group
- RG R. Jahn (Laboratory of Neurobiology)
RG Urlaub (Bioanalytische Massenspektrometrie) - External URL
- https://sfb1286.uni-goettingen.de/literature/publications/156
- eISSN
- 2041-1723
- Language
- English