Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing

  1. Lauren K Strohacker
  2. Douglas R Mackay
  3. Madeline A Whitney
  4. Genevieve C Couldwell
  5. Wesley I Sundquist  Is a corresponding author
  6. Katharine S Ullman  Is a corresponding author
  1. University of Utah, United States
  2. University of Utah School of Medicine, United States

Abstract

The abscission checkpoint regulates the ESCRT membrane fission machinery and thereby delays cytokinetic abscission to protect genomic integrity in response to residual mitotic errors. The checkpoint is maintained by Aurora B kinase, which phosphorylates multiple targets, including CHMP4C, a regulatory ESCRT-III subunit necessary for this checkpoint. We now report the discovery that cytoplasmic abscission checkpoint bodies (ACBs) containing phospho-Aurora B and tri-phospho-CHMP4C develop during an active checkpoint. ACBs are derived from Mitotic Interchromatin Granules (MIGs), transient mitotic structures whose components are housed in splicing-related nuclear speckles during interphase. ACB formation requires CHMP4C, and the ESCRT factor ALIX also contributes. ACB formation is conserved across cell types and under multiple circumstances that activate the checkpoint. Finally, ACBs retain a population of ALIX, and their presence correlates with delayed abscission and delayed recruitment of ALIX to the midbody where it would normally promote abscission. Thus, a cytoplasmic mechanism helps regulate midbody machinery to delay abscission.

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All data reported in this study are included in source data files for each figure.

Article and author information

Author details

  1. Lauren K Strohacker

    Biochemistry and Oncological Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  2. Douglas R Mackay

    Oncological Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  3. Madeline A Whitney

    Oncological Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  4. Genevieve C Couldwell

    Oncological Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  5. Wesley I Sundquist

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    wes@biochem.utah.edu
    Competing interests
    Wesley I Sundquist, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9988-6021
  6. Katharine S Ullman

    Oncological Sciences, University of Utah, Salt Lake City, United States
    For correspondence
    katharine.ullman@hci.utah.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3693-2830

Funding

National Institutes of Health (NIH R01GM112080)

  • Wesley I Sundquist
  • Katharine S Ullman

Huntsman Cancer Foundation (CRR award)

  • Wesley I Sundquist
  • Katharine S Ullman

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

Copyright

© 2021, Strohacker 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. Lauren K Strohacker
  2. Douglas R Mackay
  3. Madeline A Whitney
  4. Genevieve C Couldwell
  5. Wesley I Sundquist
  6. Katharine S Ullman
(2021)
Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing
eLife 10:e63743.
https://doi.org/10.7554/eLife.63743

Share this article

https://doi.org/10.7554/eLife.63743

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