Centrioles control the capacity, but not the specificity, of cytotoxic T cell killing Journal Article
| Authors: | Tamzalit, F.; Tran, D.; Jin, W.; Boyko, V.; Bazzi, H.; Kepecs, A.; Kam, L. C.; Anderson, K. V.; Huse, M. |
| Article Title: | Centrioles control the capacity, but not the specificity, of cytotoxic T cell killing |
| Abstract: | Immunological synapse formation between cytotoxic T lymphocytes (CTLs) and the target cells they aim to destroy is accompanied by reorientation of the CTL centrosome to a position beneath the synaptic membrane. Centrosome polarization is thought to enhance the potency and specificity of killing by driving lytic granule fusion at the synapse and thereby the release of perforin and granzymes toward the target cell. To test this model, we employed a genetic strategy to delete centrioles, the core structural components of the centrosome. Centriole deletion altered microtubule architecture as expected but surprisingly had no effect on lytic granule polarization and directional secretion. Nevertheless, CTLs lacking centrioles did display substantially reduced killing potential, which was associated with defects in both lytic granule biogenesis and synaptic actin remodeling. These results reveal an unexpected role for the intact centrosome in controlling the capacity but not the specificity of cytotoxic killing. © 2020 National Academy of Sciences. All rights reserved. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; cytotoxicity; cell specificity; cytotoxic t lymphocyte; cytoplasm; immunomodulation; microtubule; cell mediated cytotoxicity; centriole; centrosome; t cell; cell ultrastructure; cellular parameters; priority journal; article; organelle biogenesis; actin remodeling; cellular secretion; lytic granule |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 117 |
| Issue: | 8 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2020-02-25 |
| Start Page: | 4310 |
| End Page: | 4319 |
| Language: | English |
| DOI: | 10.1073/pnas.1913220117 |
| PUBMED: | 32041868 |
| PROVIDER: | scopus |
| PMCID: | PMC7049148 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2020 -- Source: Scopus |
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