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A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage
The ability to proliferate is a common feature of most T-cell populations. However, proliferation follows different cell-cycle dynamics and is coupled to different functional outcomes according to T-cell subsets. Whether the mitotic machineries supporting these qualitatively distinct proliferative r...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797186/ https://www.ncbi.nlm.nih.gov/pubmed/36519536 http://dx.doi.org/10.7554/eLife.80277 |
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author | Argenty, Jérémy Rouquié, Nelly Bories, Cyrielle Mélique, Suzanne Duplan-Eche, Valérie Saoudi, Abdelhadi Fazilleau, Nicolas Lesourne, Renaud |
author_facet | Argenty, Jérémy Rouquié, Nelly Bories, Cyrielle Mélique, Suzanne Duplan-Eche, Valérie Saoudi, Abdelhadi Fazilleau, Nicolas Lesourne, Renaud |
author_sort | Argenty, Jérémy |
collection | PubMed |
description | The ability to proliferate is a common feature of most T-cell populations. However, proliferation follows different cell-cycle dynamics and is coupled to different functional outcomes according to T-cell subsets. Whether the mitotic machineries supporting these qualitatively distinct proliferative responses are identical remains unknown. Here, we show that disruption of the microtubule-associated protein LIS1 in mouse models leads to proliferative defects associated with a blockade of T-cell development after β-selection and of peripheral CD4+ T-cell expansion after antigen priming. In contrast, cell divisions in CD8+ T cells occurred independently of LIS1 following T-cell antigen receptor stimulation, although LIS1 was required for proliferation elicited by pharmacological activation. In thymocytes and CD4+ T cells, LIS1 deficiency did not affect signaling events leading to activation but led to an interruption of proliferation after the initial round of division and to p53-induced cell death. Proliferative defects resulted from a mitotic failure, characterized by the presence of extra-centrosomes and the formation of multipolar spindles, causing abnormal chromosomes congression during metaphase and separation during telophase. LIS1 was required to stabilize dynein/dynactin complexes, which promote chromosome attachment to mitotic spindles and ensure centrosome integrity. Together, these results suggest that proliferative responses are supported by distinct mitotic machineries across T-cell subsets. |
format | Online Article Text |
id | pubmed-9797186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-97971862022-12-29 A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage Argenty, Jérémy Rouquié, Nelly Bories, Cyrielle Mélique, Suzanne Duplan-Eche, Valérie Saoudi, Abdelhadi Fazilleau, Nicolas Lesourne, Renaud eLife Cell Biology The ability to proliferate is a common feature of most T-cell populations. However, proliferation follows different cell-cycle dynamics and is coupled to different functional outcomes according to T-cell subsets. Whether the mitotic machineries supporting these qualitatively distinct proliferative responses are identical remains unknown. Here, we show that disruption of the microtubule-associated protein LIS1 in mouse models leads to proliferative defects associated with a blockade of T-cell development after β-selection and of peripheral CD4+ T-cell expansion after antigen priming. In contrast, cell divisions in CD8+ T cells occurred independently of LIS1 following T-cell antigen receptor stimulation, although LIS1 was required for proliferation elicited by pharmacological activation. In thymocytes and CD4+ T cells, LIS1 deficiency did not affect signaling events leading to activation but led to an interruption of proliferation after the initial round of division and to p53-induced cell death. Proliferative defects resulted from a mitotic failure, characterized by the presence of extra-centrosomes and the formation of multipolar spindles, causing abnormal chromosomes congression during metaphase and separation during telophase. LIS1 was required to stabilize dynein/dynactin complexes, which promote chromosome attachment to mitotic spindles and ensure centrosome integrity. Together, these results suggest that proliferative responses are supported by distinct mitotic machineries across T-cell subsets. eLife Sciences Publications, Ltd 2022-12-15 /pmc/articles/PMC9797186/ /pubmed/36519536 http://dx.doi.org/10.7554/eLife.80277 Text en © 2022, Argenty et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Argenty, Jérémy Rouquié, Nelly Bories, Cyrielle Mélique, Suzanne Duplan-Eche, Valérie Saoudi, Abdelhadi Fazilleau, Nicolas Lesourne, Renaud A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage |
title | A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage |
title_full | A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage |
title_fullStr | A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage |
title_full_unstemmed | A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage |
title_short | A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage |
title_sort | selective lis1 requirement for mitotic spindle assembly discriminates distinct t-cell division mechanisms within the t-cell lineage |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797186/ https://www.ncbi.nlm.nih.gov/pubmed/36519536 http://dx.doi.org/10.7554/eLife.80277 |
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