1. Cell Biology

Torsin ATPases influence chromatin interaction of the Torsin regulator LAP1

  1. Naemi Luithle
  2. Jelmi uit de Bos
  3. Ruud Hovius
  4. Daria Maslennikova
  5. Renard TM Lewis
  6. Rosemarie Ungricht
  7. Beat Fierz
  8. Ulrike Kutay  Is a corresponding author
  1. ETH Zürich, Switzerland
  2. EPFL, Switzerland
  3. ETH Zurich, Switzerland
https://doi.org/10.7554/eLife.63614
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  1. Naemi Luithle
  2. Jelmi uit de Bos
  3. Ruud Hovius
  4. Daria Maslennikova
  5. Renard TM Lewis
  6. Rosemarie Ungricht
  7. Beat Fierz
  8. Ulrike Kutay
(2020)
Torsin ATPases influence chromatin interaction of the Torsin regulator LAP1
eLife 9:e63614.
https://doi.org/10.7554/eLife.63614
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Abstract

The inner nuclear membrane is functionalized by diverse transmembrane proteins that associate with nuclear lamins and/or chromatin. When cells enter mitosis, membrane-chromatin contacts must be broken to allow for proper chromosome segregation; yet how this occurs remains ill-understood. Unexpectedly, we observed that an imbalance in the levels of the lamina-associated polypeptide 1 (LAP1), an activator of ER-resident Torsin AAA+-ATPases, causes a failure in membrane removal from mitotic chromatin, accompanied by chromosome segregation errors and changes in post-mitotic nuclear morphology. These defects are dependent on a hitherto unknown chromatin-binding region of LAP1 that we have delineated. LAP1-induced NE abnormalities are efficiently suppressed by expression of wild-type but not ATPase-deficient Torsins. Furthermore, a dominant-negative Torsin induces chromosome segregation defects in a LAP1-dependent manner. These results indicate that association of LAP1 with chromatin in the nucleus can be modulated by Torsins in the perinuclear space, shedding new light on the LAP1-Torsin interplay.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Author details

  1. Naemi Luithle

    Institute of Biochemistry, ETH Zürich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.

  2. Jelmi uit de Bos

    Institute of Biochemistry, ETH Zürich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8807-3284

  3. Ruud Hovius

    Institute of Chemical Sciences and Engineering, EPFL, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9258-6587

  4. Daria Maslennikova

    Institute of Biochemistry, ETH Zürich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.

  5. Renard TM Lewis

    Institute of Biochemistry, ETH Zürich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.

  6. Rosemarie Ungricht

    Institute of Biochemistry, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.

  7. Beat Fierz

    Institute of Chemical Sciences and Engineering, EPFL, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.

  8. Ulrike Kutay

    Institute of Biochemistry, ETH Zürich, Zurich, Switzerland
    For correspondence
    ulrike.kutay@bc.biol.ethz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8257-7465

Funding

Swiss National Science Foundation (310030_184801)

  • Ulrike Kutay

EPFL

  • Beat Fierz

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

Reviewing Editor

  1. Megan C King, Yale School of Medicine, United States

Version history

  1. Received: September 30, 2020
  2. Accepted: December 15, 2020
  3. Accepted Manuscript published: December 15, 2020 (version 1)
  4. Version of Record published: December 30, 2020 (version 2)

Copyright

© 2020, Luithle 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. Naemi Luithle
  2. Jelmi uit de Bos
  3. Ruud Hovius
  4. Daria Maslennikova
  5. Renard TM Lewis
  6. Rosemarie Ungricht
  7. Beat Fierz
  8. Ulrike Kutay
(2020)
Torsin ATPases influence chromatin interaction of the Torsin regulator LAP1
eLife 9:e63614.
https://doi.org/10.7554/eLife.63614

Share this article

https://doi.org/10.7554/eLife.63614

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