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Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase

During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then corr...

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Autores principales: Parmar, Sneha, Gonzalez, Samuel J., Heckel, Julia M., Mukherjee, Soumya, McClellan, Mark, Clarke, Duncan J., Johansson, Marnie, Tank, Damien, Geisness, Athena, Wood, David K., Gardner, Melissa K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182774/
https://www.ncbi.nlm.nih.gov/pubmed/37166419
http://dx.doi.org/10.1083/jcb.202202085
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author Parmar, Sneha
Gonzalez, Samuel J.
Heckel, Julia M.
Mukherjee, Soumya
McClellan, Mark
Clarke, Duncan J.
Johansson, Marnie
Tank, Damien
Geisness, Athena
Wood, David K.
Gardner, Melissa K.
author_facet Parmar, Sneha
Gonzalez, Samuel J.
Heckel, Julia M.
Mukherjee, Soumya
McClellan, Mark
Clarke, Duncan J.
Johansson, Marnie
Tank, Damien
Geisness, Athena
Wood, David K.
Gardner, Melissa K.
author_sort Parmar, Sneha
collection PubMed
description During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches improperly attached kinetochores from their microtubules. However, the sequence of events leading up to these detachment events remains unknown. In this study, we used microfluidics to sustain and observe low-tension budding yeast metaphase spindles over multiple hours, allowing us to elucidate the tension history prior to a detachment event. We found that, under conditions in which kinetochore phosphorylation weakens low-tension kinetochore-microtubule connections, the mechanical forces produced via the dynamic growth and shortening of microtubules is required to efficiently facilitate detachment events. Our findings underscore the critical role of robust kinetochore microtubule dynamics in ensuring the fidelity of chromosome segregation during mitosis.
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spelling pubmed-101827742023-11-11 Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase Parmar, Sneha Gonzalez, Samuel J. Heckel, Julia M. Mukherjee, Soumya McClellan, Mark Clarke, Duncan J. Johansson, Marnie Tank, Damien Geisness, Athena Wood, David K. Gardner, Melissa K. J Cell Biol Article During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches improperly attached kinetochores from their microtubules. However, the sequence of events leading up to these detachment events remains unknown. In this study, we used microfluidics to sustain and observe low-tension budding yeast metaphase spindles over multiple hours, allowing us to elucidate the tension history prior to a detachment event. We found that, under conditions in which kinetochore phosphorylation weakens low-tension kinetochore-microtubule connections, the mechanical forces produced via the dynamic growth and shortening of microtubules is required to efficiently facilitate detachment events. Our findings underscore the critical role of robust kinetochore microtubule dynamics in ensuring the fidelity of chromosome segregation during mitosis. Rockefeller University Press 2023-05-11 /pmc/articles/PMC10182774/ /pubmed/37166419 http://dx.doi.org/10.1083/jcb.202202085 Text en © 2023 Parmar et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Parmar, Sneha
Gonzalez, Samuel J.
Heckel, Julia M.
Mukherjee, Soumya
McClellan, Mark
Clarke, Duncan J.
Johansson, Marnie
Tank, Damien
Geisness, Athena
Wood, David K.
Gardner, Melissa K.
Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase
title Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase
title_full Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase
title_fullStr Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase
title_full_unstemmed Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase
title_short Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase
title_sort robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182774/
https://www.ncbi.nlm.nih.gov/pubmed/37166419
http://dx.doi.org/10.1083/jcb.202202085
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