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Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion

The expulsion of dying epithelial cells requires well-orchestrated remodelling steps to maintain tissue sealing. This process, named cell extrusion, has been mostly analysed through the study of actomyosin regulation. Yet, the mechanistic relationship between caspase activation and cell extrusion is...

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Autores principales: Villars, Alexis, Matamoro-Vidal, Alexis, Levillayer, Florence, Levayer, Romain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233712/
https://www.ncbi.nlm.nih.gov/pubmed/35752632
http://dx.doi.org/10.1038/s41467-022-31266-8
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author Villars, Alexis
Matamoro-Vidal, Alexis
Levillayer, Florence
Levayer, Romain
author_facet Villars, Alexis
Matamoro-Vidal, Alexis
Levillayer, Florence
Levayer, Romain
author_sort Villars, Alexis
collection PubMed
description The expulsion of dying epithelial cells requires well-orchestrated remodelling steps to maintain tissue sealing. This process, named cell extrusion, has been mostly analysed through the study of actomyosin regulation. Yet, the mechanistic relationship between caspase activation and cell extrusion is still poorly understood. Using the Drosophila pupal notum, a single layer epithelium where extrusions are caspase-dependent, we showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration and dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion, while microtubule stabilisation strongly impairs cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting step of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation.
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spelling pubmed-92337122022-06-27 Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion Villars, Alexis Matamoro-Vidal, Alexis Levillayer, Florence Levayer, Romain Nat Commun Article The expulsion of dying epithelial cells requires well-orchestrated remodelling steps to maintain tissue sealing. This process, named cell extrusion, has been mostly analysed through the study of actomyosin regulation. Yet, the mechanistic relationship between caspase activation and cell extrusion is still poorly understood. Using the Drosophila pupal notum, a single layer epithelium where extrusions are caspase-dependent, we showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration and dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion, while microtubule stabilisation strongly impairs cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting step of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation. Nature Publishing Group UK 2022-06-25 /pmc/articles/PMC9233712/ /pubmed/35752632 http://dx.doi.org/10.1038/s41467-022-31266-8 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Villars, Alexis
Matamoro-Vidal, Alexis
Levillayer, Florence
Levayer, Romain
Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
title Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
title_full Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
title_fullStr Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
title_full_unstemmed Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
title_short Microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
title_sort microtubule disassembly by caspases is an important rate-limiting step of cell extrusion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233712/
https://www.ncbi.nlm.nih.gov/pubmed/35752632
http://dx.doi.org/10.1038/s41467-022-31266-8
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