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Mechanical coupling coordinates microtubule growth

During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to be...

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Autores principales: Leeds, Bonnibelle K., Kostello, Katelyn F., Liu, Yuna Y., Nelson, Christian R., Biggins, Sue, Asbury, Charles L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614740/
https://www.ncbi.nlm.nih.gov/pubmed/37905093
http://dx.doi.org/10.1101/2023.06.29.547092
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author Leeds, Bonnibelle K.
Kostello, Katelyn F.
Liu, Yuna Y.
Nelson, Christian R.
Biggins, Sue
Asbury, Charles L.
author_facet Leeds, Bonnibelle K.
Kostello, Katelyn F.
Liu, Yuna Y.
Nelson, Christian R.
Biggins, Sue
Asbury, Charles L.
author_sort Leeds, Bonnibelle K.
collection PubMed
description During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to behave as a single unit. This exquisite coordination might be achieved biochemically, via selective binding of polymerases and depolymerases, or mechanically, because k-fiber microtubules are coupled through a shared load that influences their growth. Here, we use a novel dual laser trap assay to show that microtubule pairs growing in vitro are coordinated by mechanical coupling. Kinetic analyses show that microtubule growth is interrupted by stochastic, force-dependent pauses and indicate persistent heterogeneity in growth speed during non-pauses. A simple model incorporating both force-dependent pausing and persistent growth speed heterogeneity explains the measured coordination of microtubule pairs without any free fit parameters. Our findings illustrate how microtubule growth may be synchronized during mitosis and provide a basis for modeling k-fiber bundles with three or more microtubules, as found in many eukaryotes.
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spelling pubmed-106147402023-10-31 Mechanical coupling coordinates microtubule growth Leeds, Bonnibelle K. Kostello, Katelyn F. Liu, Yuna Y. Nelson, Christian R. Biggins, Sue Asbury, Charles L. bioRxiv Article During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to behave as a single unit. This exquisite coordination might be achieved biochemically, via selective binding of polymerases and depolymerases, or mechanically, because k-fiber microtubules are coupled through a shared load that influences their growth. Here, we use a novel dual laser trap assay to show that microtubule pairs growing in vitro are coordinated by mechanical coupling. Kinetic analyses show that microtubule growth is interrupted by stochastic, force-dependent pauses and indicate persistent heterogeneity in growth speed during non-pauses. A simple model incorporating both force-dependent pausing and persistent growth speed heterogeneity explains the measured coordination of microtubule pairs without any free fit parameters. Our findings illustrate how microtubule growth may be synchronized during mitosis and provide a basis for modeling k-fiber bundles with three or more microtubules, as found in many eukaryotes. Cold Spring Harbor Laboratory 2023-10-17 /pmc/articles/PMC10614740/ /pubmed/37905093 http://dx.doi.org/10.1101/2023.06.29.547092 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Leeds, Bonnibelle K.
Kostello, Katelyn F.
Liu, Yuna Y.
Nelson, Christian R.
Biggins, Sue
Asbury, Charles L.
Mechanical coupling coordinates microtubule growth
title Mechanical coupling coordinates microtubule growth
title_full Mechanical coupling coordinates microtubule growth
title_fullStr Mechanical coupling coordinates microtubule growth
title_full_unstemmed Mechanical coupling coordinates microtubule growth
title_short Mechanical coupling coordinates microtubule growth
title_sort mechanical coupling coordinates microtubule growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614740/
https://www.ncbi.nlm.nih.gov/pubmed/37905093
http://dx.doi.org/10.1101/2023.06.29.547092
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