Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles
Abstract
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.
Article and author information
Author details
Funding
Human Frontier Science Program (CDA00074/2014)
- Jan Brugues
European Molecular Biology Organization (ALTF 483-2016)
- David Oriola
Deutsche Forschungsgemeinschaft
- Franziska Decker
Max-Planck-Gesellschaft (Open-access funding)
- Franziska Decker
- David Oriola
- Benjamin Dalton
- Jan Brugues
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany
Ethics
Animal experimentation: All animals were handled according to the directive 2010/63/EU on the protection of animals used for scientific purposes, and the german animal welfare law under the license document number DD24-5131/367/9 from the Landesdirektion Sachsen (Dresden) - Section 24D.
Version history
- Received: August 11, 2017
- Accepted: January 9, 2018
- Accepted Manuscript published: January 11, 2018 (version 1)
- Version of Record published: February 15, 2018 (version 2)
- Version of Record updated: February 19, 2018 (version 3)
Copyright
© 2018, Decker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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