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Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization

The spindle is a dynamic intracellular structure self-organized from microtubules and microtubule-associated proteins. The spindle’s bipolar morphology is essential for the faithful segregation of chromosomes during cell division, and it is robustly maintained by multifaceted mechanisms. However, ab...

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Autores principales: Fukuyama, Tatsuya, Yan, Lucan, Tanaka, Masahito, Yamaoka, Megumi, Saito, Kei, Ti, Shih-Chieh, Liao, Chung-Chi, Hsia, Kuo-Chiang, Maeda, Yusuke T., Shimamoto, Yuta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636915/
https://www.ncbi.nlm.nih.gov/pubmed/36282919
http://dx.doi.org/10.1073/pnas.2209053119
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author Fukuyama, Tatsuya
Yan, Lucan
Tanaka, Masahito
Yamaoka, Megumi
Saito, Kei
Ti, Shih-Chieh
Liao, Chung-Chi
Hsia, Kuo-Chiang
Maeda, Yusuke T.
Shimamoto, Yuta
author_facet Fukuyama, Tatsuya
Yan, Lucan
Tanaka, Masahito
Yamaoka, Megumi
Saito, Kei
Ti, Shih-Chieh
Liao, Chung-Chi
Hsia, Kuo-Chiang
Maeda, Yusuke T.
Shimamoto, Yuta
author_sort Fukuyama, Tatsuya
collection PubMed
description The spindle is a dynamic intracellular structure self-organized from microtubules and microtubule-associated proteins. The spindle’s bipolar morphology is essential for the faithful segregation of chromosomes during cell division, and it is robustly maintained by multifaceted mechanisms. However, abnormally shaped spindles, such as multipolar spindles, can stochastically arise in a cell population and cause chromosome segregation errors. The physical basis of how microtubules fail in bipolarization and occasionally favor nonbipolar assembly is poorly understood. Here, using live fluorescence imaging and quantitative shape analysis in Xenopus egg extracts, we find that spindles of varied shape morphologies emerge through nonrandom, bistable self-organization paths, one leading to a bipolar and the other leading to a multipolar phenotype. The bistability defines the spindle’s unique morphological growth dynamics linked to each shape phenotype and can be promoted by a locally distorted microtubule flow that arises within premature structures. We also find that bipolar and multipolar spindles are stable at the steady-state in bulk but can infrequently switch between the two phenotypes. Our microneedle-based physical manipulation further demonstrates that a transient force perturbation applied near the assembled pole can trigger the phenotypic switching, revealing the mechanical plasticity of the spindle. Together with molecular perturbation of kinesin-5 and augmin, our data propose the physical and molecular bases underlying the emergence of spindle-shape variation, which influences chromosome segregation fidelity during cell division.
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spelling pubmed-96369152023-04-25 Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization Fukuyama, Tatsuya Yan, Lucan Tanaka, Masahito Yamaoka, Megumi Saito, Kei Ti, Shih-Chieh Liao, Chung-Chi Hsia, Kuo-Chiang Maeda, Yusuke T. Shimamoto, Yuta Proc Natl Acad Sci U S A Biological Sciences The spindle is a dynamic intracellular structure self-organized from microtubules and microtubule-associated proteins. The spindle’s bipolar morphology is essential for the faithful segregation of chromosomes during cell division, and it is robustly maintained by multifaceted mechanisms. However, abnormally shaped spindles, such as multipolar spindles, can stochastically arise in a cell population and cause chromosome segregation errors. The physical basis of how microtubules fail in bipolarization and occasionally favor nonbipolar assembly is poorly understood. Here, using live fluorescence imaging and quantitative shape analysis in Xenopus egg extracts, we find that spindles of varied shape morphologies emerge through nonrandom, bistable self-organization paths, one leading to a bipolar and the other leading to a multipolar phenotype. The bistability defines the spindle’s unique morphological growth dynamics linked to each shape phenotype and can be promoted by a locally distorted microtubule flow that arises within premature structures. We also find that bipolar and multipolar spindles are stable at the steady-state in bulk but can infrequently switch between the two phenotypes. Our microneedle-based physical manipulation further demonstrates that a transient force perturbation applied near the assembled pole can trigger the phenotypic switching, revealing the mechanical plasticity of the spindle. Together with molecular perturbation of kinesin-5 and augmin, our data propose the physical and molecular bases underlying the emergence of spindle-shape variation, which influences chromosome segregation fidelity during cell division. National Academy of Sciences 2022-10-25 2022-11-01 /pmc/articles/PMC9636915/ /pubmed/36282919 http://dx.doi.org/10.1073/pnas.2209053119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Fukuyama, Tatsuya
Yan, Lucan
Tanaka, Masahito
Yamaoka, Megumi
Saito, Kei
Ti, Shih-Chieh
Liao, Chung-Chi
Hsia, Kuo-Chiang
Maeda, Yusuke T.
Shimamoto, Yuta
Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization
title Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization
title_full Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization
title_fullStr Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization
title_full_unstemmed Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization
title_short Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization
title_sort morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle self-organization
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636915/
https://www.ncbi.nlm.nih.gov/pubmed/36282919
http://dx.doi.org/10.1073/pnas.2209053119
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