Stable Pom1 clusters form a glucose-modulated concentration gradient that regulates mitotic entry

  1. Corey A H Allard
  2. Hannah E Opalko
  3. James B Moseley  Is a corresponding author
  1. The Geisel School of Medicine at Dartmouth, United States

Abstract

Control of cell size requires molecular size sensors that are coupled to the cell cycle. Rod-shaped fission yeast cells divide at a threshold size partly due to Cdr2 kinase, which forms nodes at the medial cell cortex where it inhibits the Cdk1-inhibitor Wee1. Pom1 kinase phosphorylates and inhibits Cdr2, and forms cortical concentration gradients from cell poles. Pom1 inhibits Cdr2 signaling to Wee1 specifically in small cells, but the time and place of their regulatory interactions were unclear. We show that Pom1 forms stable oligomeric clusters that dynamically sample the cell cortex. Binding frequency is patterned into a concentration gradient by the polarity landmarks Tea1 and Tea4. Pom1 clusters colocalize with Cdr2 nodes, forming a glucose-modulated inhibitory threshold against node activation. Our work reveals how Pom1-Cdr2-Wee1 operates in multiprotein clusters at the cortex to promote mitotic entry at a cell size that can be modified by nutrient availability.

Data availability

We have included all relevant data in the manuscript and supporting files.

Article and author information

Author details

  1. Corey A H Allard

    Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hannah E Opalko

    Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. James B Moseley

    Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, United States
    For correspondence
    james.b.moseley@dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7354-7416

Funding

National Institute of General Medical Sciences (R01GM099774)

  • James B Moseley

American Cancer Society (RSG-15-140-01)

  • James B Moseley

National Institute of General Medical Sciences (T32GM008704)

  • Corey A H Allard

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mohan K Balasubramanian, University of Warwick, United Kingdom

Publication history

  1. Received: February 12, 2019
  2. Accepted: May 2, 2019
  3. Accepted Manuscript published: May 3, 2019 (version 1)
  4. Version of Record published: May 17, 2019 (version 2)

Copyright

© 2019, Allard 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. Corey A H Allard
  2. Hannah E Opalko
  3. James B Moseley
(2019)
Stable Pom1 clusters form a glucose-modulated concentration gradient that regulates mitotic entry
eLife 8:e46003.
https://doi.org/10.7554/eLife.46003

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