Please use this identifier to cite or link to this item:
doi:10.22028/D291-36382
Title: | Identification of distinct cytotoxic granules as the origin of supramolecular attack particles in T lymphocytes |
Author(s): | Chang, Hsin-Fang Schirra, Claudia Ninov, Momchil Hahn, Ulrike Ravichandran, Keerthana Krause, Elmar Becherer, Ute Bálint, Štefan Harkiolaki, Maria Urlaub, Henning Valitutti, Salvatore Baldari, Cosima T. Dustin, Michael L. Jahn, Reinhard Rettig, Jens |
Language: | English |
Title: | Nature Communications |
Volume: | 13 |
Issue: | 1 |
Publisher/Platform: | Springer Nature |
Year of Publication: | 2022 |
Free key words: | Cytotoxic T cells Imaging the immune system Lysosomes |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
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. |
DOI of the first publication: | 10.1038/s41467-022-28596-y |
URL of the first publication: | https://www.nature.com/articles/s41467-022-28596-y |
Link to this record: | urn:nbn:de:bsz:291--ds-363828 hdl:20.500.11880/33031 http://dx.doi.org/10.22028/D291-36382 |
ISSN: | 2041-1723 |
Date of registration: | 8-Jun-2022 |
Description of the related object: | Supplementary information |
Related object: | https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM2_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM3_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM4_ESM.xlsx https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM5_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM6_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM7_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM8_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-28596-y/MediaObjects/41467_2022_28596_MOESM9_ESM.pdf |
Faculty: | M - Medizinische Fakultät |
Department: | M - Physiologie |
Professorship: | M - Prof. Dr. Jens Rettig |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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s41467-022-28596-y.pdf | 4,07 MB | Adobe PDF | View/Open |
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