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Ataxin-7 and Non-stop coordinate SCAR protein levels, subcellular localization, and actin cytoskeleton organization

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Cite this article as: eLife 2019;8:e49677 doi: 10.7554/eLife.49677

Abstract

Atxn7, a subunit of SAGA chromatin remodeling complex, is subject to polyglutamine expansion at the amino terminus, causing spinocerebellar ataxia type 7 (SCA7), a progressive retinal and neurodegenerative disease. Within SAGA, the Atxn7 amino terminus anchors Non-stop, a deubiquitinase, to the complex. To understand the scope of Atxn7-dependent regulation of Non-stop, substrates of the deubiquitinase were sought. This revealed Non-stop, dissociated from Atxn7, interacts with Arp2/3 and WAVE regulatory complexes (WRC), which control actin cytoskeleton assembly. There, Non-stop countered polyubiquitination and proteasomal degradation of WRC subunit SCAR. Dependent on conserved WRC interacting receptor sequences (WIRS), Non-stop augmentation increased protein levels, and directed subcellular localization, of SCAR, decreasing cell area and number of protrusions. In vivo, heterozygous mutation of Atxn7 rescued haploinsufficiency of SCAR, but heterozygous mutation of SCAR did not significantly rescue knockdown of Atxn7.

Article and author information

Author details

  1. Veronica Cloud

    School of Biological Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ada Thapa

    School of Biological and Chemical Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Pedro Morales-Sosa

    School of Biological and Chemical Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tayla Miller

    School of Biological and Chemical Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sara A Miller

    School of Biological Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel Holsapple

    School of Biological Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Paige Gerhart

    School of Biological and Chemical Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Elaheh Momtahan

    School of Biological Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jarrid L Jack

    School of Biological Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Edgardo Leiva

    School of Biological Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Sarah R Rapp

    School of Biological Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Lauren G Shelton

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Richard A Pierce

    School of Biological and Chemical Sciences, University of Missouri - Kansas City, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Skylar Martin-Brown

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Laurence Florens

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Michael P Washburn

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7568-2585
  17. Ryan D Mohan

    School of Biological and Chemical Sciences, University of Missouri - Kansas City, Kansas City, United States
    For correspondence
    Mohanrd@umkc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7624-4605

Funding

National Institutes of Health (NIGMS grant 5R35GM118068)

  • Ryan D Mohan

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

Reviewing Editor

  1. Irwin Davidson, Institut de Génétique et de Biologie Moléculaire et Cellulaire, France

Publication history

  1. Received: June 25, 2019
  2. Accepted: July 22, 2019
  3. Accepted Manuscript published: July 26, 2019 (version 1)
  4. Version of Record published: August 14, 2019 (version 2)

Copyright

© 2019, Cloud 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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