Control of nuclear size by osmotic forces in Schizosaccharomyces pombe

  1. Joël Lemière
  2. Paula Real-Calderon
  3. Liam J Holt
  4. Thomas G Fai  Is a corresponding author
  5. Fred Chang  Is a corresponding author
  1. University of California, San Francisco, United States
  2. New York University Langone Medical Center, United States
  3. Brandeis University, United States

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

  1. Joël Lemière

    University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9017-1959
  2. Paula Real-Calderon

    University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Liam J Holt

    Institute for Systems Genetics, New York University Langone Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Thomas G Fai

    Department of Mathematics, Brandeis University, Waltham, United States
    For correspondence
    tfai@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0383-5217
  5. Fred Chang

    University of California, San Francisco, San Francisco, United States
    For correspondence
    fred.chang@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8907-3286

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.

Reviewing Editor

  1. Naama Barkai, Weizmann Institute of Science, Israel

Publication history

  1. Received: December 3, 2021
  2. Preprint posted: December 7, 2021 (view preprint)
  3. Accepted: July 19, 2022
  4. Accepted Manuscript published: July 20, 2022 (version 1)

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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  1. Joël Lemière
  2. Paula Real-Calderon
  3. Liam J Holt
  4. Thomas G Fai
  5. Fred Chang
(2022)
Control of nuclear size by osmotic forces in Schizosaccharomyces pombe
eLife 11:e76075.
https://doi.org/10.7554/eLife.76075

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