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Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles

Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that micro...

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Detalles Bibliográficos
Autores principales: Decker, Franziska, Oriola, David, Dalton, Benjamin, Brugués, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814149/
https://www.ncbi.nlm.nih.gov/pubmed/29323637
http://dx.doi.org/10.7554/eLife.31149
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author Decker, Franziska
Oriola, David
Dalton, Benjamin
Brugués, Jan
author_facet Decker, Franziska
Oriola, David
Dalton, Benjamin
Brugués, Jan
author_sort Decker, Franziska
collection PubMed
description Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting.
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spelling pubmed-58141492018-02-22 Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles Decker, Franziska Oriola, David Dalton, Benjamin Brugués, Jan eLife Structural Biology and Molecular Biophysics Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting. eLife Sciences Publications, Ltd 2018-01-11 /pmc/articles/PMC5814149/ /pubmed/29323637 http://dx.doi.org/10.7554/eLife.31149 Text en © 2018, Decker 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 Structural Biology and Molecular Biophysics
Decker, Franziska
Oriola, David
Dalton, Benjamin
Brugués, Jan
Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles
title Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles
title_full Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles
title_fullStr Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles
title_full_unstemmed Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles
title_short Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles
title_sort autocatalytic microtubule nucleation determines the size and mass of xenopus laevis egg extract spindles
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814149/
https://www.ncbi.nlm.nih.gov/pubmed/29323637
http://dx.doi.org/10.7554/eLife.31149
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