LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior

Abstract

Lamins form stable filaments at the nuclear periphery in metazoans. Unlike B-type lamins, lamins A and C localize also in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2a). Using antibody labeling, we previously observed a depletion of nucleoplasmic A-type lamins in mouse cells lacking LAP2a. Here we show that loss of LAP2a actually causes formation of larger, biochemically stable lamin A/C structures in the nuclear interior that are inaccessible to lamin A/C antibodies. While nucleoplasmic lamin A forms from newly expressed pre-lamin A during processing and from soluble mitotic lamins in a LAP2a-independent manner, binding of LAP2a to lamins A/C during interphase inhibits formation of higher order structures, keeping nucleoplasmic lamin A/C in a mobile state independent of lamin A/C S22 phosphorylation. We propose that LAP2a is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2G-H, Figure 4A-B and Figure 6A

Article and author information

Author details

  1. Nana Naetar

    Max Perutz Labs, Medical University Vienna, Vienna, Austria
    For correspondence
    nana.naetar@univie.ac.at
    Competing interests
    The authors declare that no competing interests exist.
  2. Konstantina Georgiou

    Max Perutz Labs, Medical University Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Christian Knapp

    Max Perutz Labs, Medical University Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2463-5775
  4. Irena Bronshtein

    Physics Department and Nanotechnology Institute, Bar Ilan University, Ramt Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Elisabeth Zier

    Max Perutz Labs, Medical University Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  6. Petra Fichtinger

    Max Perutz Labs, Medical University Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Thomas Dechat

    Max Perutz Labs, Medical University Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  8. Yuval Garini

    The Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  9. Roland Foisner

    Max Perutz Labs, Medical University Vienna, Vienna, Austria
    For correspondence
    roland.foisner@meduniwien.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4734-4647

Funding

Austrian Science Fund (P26492-B20,P29713-B28,P32512-B)

  • Roland Foisner

Austrian Academy of Sciences (APART 11657)

  • Nana Naetar

Israel Science Foundation (ISF grant 1219/17)

  • Irena Bronshtein
  • Yuval Garini

European Cooperation in Science and Technology (COST-STSM-BM1002-8698,COST-STSM-BM1002-11436)

  • Thomas Dechat

European Molecular Biology Organization (ASTF 316-2011)

  • Thomas Dechat

S Grosskopf Grant

  • Irena Bronshtein
  • Yuval Garini

Austrian Academy of Sciences (ÖAW DOC 25725)

  • Konstantina Georgiou

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 28, 2020
  2. Accepted: February 18, 2021
  3. Accepted Manuscript published: February 19, 2021 (version 1)
  4. Version of Record published: March 8, 2021 (version 2)

Copyright

© 2021, Naetar 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. Nana Naetar
  2. Konstantina Georgiou
  3. Christian Knapp
  4. Irena Bronshtein
  5. Elisabeth Zier
  6. Petra Fichtinger
  7. Thomas Dechat
  8. Yuval Garini
  9. Roland Foisner
(2021)
LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior
eLife 10:e63476.
https://doi.org/10.7554/eLife.63476

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https://doi.org/10.7554/eLife.63476

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