Role of competition between polarity sites in establishing a unique front

  1. Chi-Fang Wu
  2. Jian-Geng Chiou
  3. Maria Minakova
  4. Benjamin Woods
  5. Denis Tsygankov
  6. Trevin R Zyla
  7. Natasha S Savage
  8. Timothy C Elston
  9. Daniel J Lew  Is a corresponding author
  1. Duke University School of Medicine, United States
  2. University of North Carolina at Chapel Hill, United States
  3. University of Liverpool, United Kingdom

Abstract

Polarity establishment in many cells is thought to occur via positive feedback that reinforces even tiny asymmetries in polarity protein distribution. Cdc42 and related GTPases are activated and accumulate in a patch of the cortex that defines the front of the cell. Positive feedback enables spontaneous polarization triggered by stochastic fluctuations, but as such fluctuations can occur at multiple locations, how do cells ensure that they make only one front? In polarizing cells of the model yeast Saccharomyces cerevisiae, positive feedback can trigger growth of several Cdc42 clusters at the same time, but this multi-cluster stage rapidly evolves to a single-cluster state, which then promotes bud emergence. By manipulating polarity protein dynamics, we show that resolution of multi-cluster intermediates occurs through a greedy competition between clusters to recruit and retain polarity proteins from a shared intracellular pool.

Article and author information

Author details

  1. Chi-Fang Wu

    Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jian-Geng Chiou

    Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maria Minakova

    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Benjamin Woods

    Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Denis Tsygankov

    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Trevin R Zyla

    Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Natasha S Savage

    Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Timothy C Elston

    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Daniel J Lew

    Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States
    For correspondence
    daniel.lew@duke.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Wu 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.

Metrics

  • 2,410
    views
  • 612
    downloads
  • 53
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Chi-Fang Wu
  2. Jian-Geng Chiou
  3. Maria Minakova
  4. Benjamin Woods
  5. Denis Tsygankov
  6. Trevin R Zyla
  7. Natasha S Savage
  8. Timothy C Elston
  9. Daniel J Lew
(2015)
Role of competition between polarity sites in establishing a unique front
eLife 4:e11611.
https://doi.org/10.7554/eLife.11611

Share this article

https://doi.org/10.7554/eLife.11611

Further reading

    1. Cell Biology
    2. Developmental Biology
    Deepak Adhikari, John Carroll
    Insight

    The formation of large endolysosomal structures in unfertilized eggs ensures that lysosomes remain dormant before fertilization, and then shift into clean-up mode after the egg-to-embryo transition.

    1. Cell Biology
    2. Developmental Biology
    Filip Knop, Apolena Zounarová ... Marie Macůrková
    Research Article Updated

    During Caenorhabditis elegans development, multiple cells migrate long distances or extend processes to reach their final position and/or attain proper shape. The Wnt signalling pathway stands out as one of the major coordinators of cell migration or cell outgrowth along the anterior-posterior body axis. The outcome of Wnt signalling is fine-tuned by various mechanisms including endocytosis. In this study, we show that SEL-5, the C. elegans orthologue of mammalian AP2-associated kinase AAK1, acts together with the retromer complex as a positive regulator of EGL-20/Wnt signalling during the migration of QL neuroblast daughter cells. At the same time, SEL-5 in cooperation with the retromer complex is also required during excretory canal cell outgrowth. Importantly, SEL-5 kinase activity is not required for its role in neuronal migration or excretory cell outgrowth, and neither of these processes is dependent on DPY-23/AP2M1 phosphorylation. We further establish that the Wnt proteins CWN-1 and CWN-2, together with the Frizzled receptor CFZ-2, positively regulate excretory cell outgrowth, while LIN-44/Wnt and LIN-17/Frizzled together generate a stop signal inhibiting its extension.