Control of nuclear size by osmotic forces in Schizosaccharomyces pombe
Abstract
The size of the nucleus scales robustly with cell size so that the nuclear-to-cell volume ratio (N/C ratio) is maintained during cell growth in many cell types. The mechanism responsible for this scaling remains mysterious. Previous studies have established that the N/C ratio is not determined by DNA amount but is instead influenced by factors such as nuclear envelope mechanics and nuclear transport. Here, we developed a quantitative model for nuclear size control based upon colloid osmotic pressure and tested key predictions in the fission yeast Schizosaccharomyces pombe. This model posits that the N/C ratio is determined by the numbers of macromolecules in the nucleoplasm and cytoplasm. Osmotic shift experiments showed that the fission yeast nucleus behaves as an ideal osmometer whose volume is primarily dictated by osmotic forces. Inhibition of nuclear export caused accumulation of macromolecules and an increase in crowding in the nucleoplasm, leading to nuclear swelling. We further demonstrated that the N/C ratio is maintained by a homeostasis mechanism based upon synthesis of macromolecules during growth. These studies demonstrate the functions of colloid osmotic pressure in intracellular organization and size control.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file. A source data file has been provided for Figures 2-7 and Supplementary Figures.
Article and author information
Author details
Funding
National Institutes of Health (R01 GM056836)
- Fred Chang
National Institutes of Health (R35 GM141796)
- Fred Chang
National Science Foundation (MCB-1638195)
- Fred Chang
National Science Foundation (DMS-1913093)
- Thomas G Fai
American Cancer Society
- Liam J Holt
Pershing Square Sohn Cancer Research Alliance
- Liam J Holt
National Institutes of Health (R01 GM132447)
- Liam J Holt
National Institutes of Health (R37 CA240765)
- Liam J Holt
Chan Zuckerberg Initiative
- Liam J Holt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Lemière 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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