Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Argenty, Jérémy, Rouquié, Nelly, Bories, Cyrielle, Mélique, Suzanne, Duplan-Eche, Valérie, Saoudi, Abdelhadi, Fazilleau, Nicolas, Lesourne, Renaud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
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
_version_ 1784860641623801856
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
work_keys_str_mv AT argentyjeremy aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT rouquienelly aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT boriescyrielle aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT meliquesuzanne aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT duplanechevalerie aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT saoudiabdelhadi aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT fazilleaunicolas aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT lesournerenaud aselectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT argentyjeremy selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT rouquienelly selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT boriescyrielle selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT meliquesuzanne selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT duplanechevalerie selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT saoudiabdelhadi selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT fazilleaunicolas selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage
AT lesournerenaud selectivelis1requirementformitoticspindleassemblydiscriminatesdistincttcelldivisionmechanismswithinthetcelllineage