1. Cell Biology
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Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration

  1. Jeremy S Logue  Is a corresponding author
  2. Alexander X Cartagena-Rivera
  3. Michelle A Baird
  4. Michael W Davidson
  5. Richard S Chadwick
  6. Clare M Waterman
  1. National Institutes of Health, United States
  2. Florida State University, United States
Research Article
  • Cited 42
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Cite this article as: eLife 2015;4:e08314 doi: 10.7554/eLife.08314

Abstract

Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-adhesive environment migrate in the direction of a very large 'leader bleb.' Eps8 bundling activity promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under non-adhesive confinement.

Article and author information

Author details

  1. Jeremy S Logue

    National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    For correspondence
    jeremy.logue@nih.gov
    Competing interests
    No competing interests declared.
  2. Alexander X Cartagena-Rivera

    National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  3. Michelle A Baird

    National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  4. Michael W Davidson

    National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, United States
    Competing interests
    No competing interests declared.
  5. Richard S Chadwick

    National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  6. Clare M Waterman

    National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    Clare M Waterman, Reviewing editor for eLife.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Publication history

  1. Received: April 24, 2015
  2. Accepted: July 10, 2015
  3. Accepted Manuscript published: July 11, 2015 (version 1)
  4. Accepted Manuscript updated: July 14, 2015 (version 2)
  5. Version of Record published: August 3, 2015 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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