Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics

Abstract

Nuclear transport is facilitated by the Nuclear Pore Complex (NPC) and is essential for life in eukaryotes. The NPC is a long-lived and exceptionally large structure. We asked whether NPC quality control is compromised in aging mitotic cells. Our images of single yeast cells during aging, show that the abundance of several NPC components and NPC assembly factors decreases. Additionally, the single cell life histories reveal that cells that better maintain those components are longer lived. The presence of herniations at the nuclear envelope of aged cells suggests that misassembled NPCs are accumulated in aged cells. Aged cells show decreased dynamics of transcription factor shuttling and increased nuclear compartmentalisation. These functional changes are likely caused by the presence of misassembled NPCs, as we find that two NPC assembly mutants show similar transport phenotypes as aged cells. We conclude that NPC interphase assembly is a major challenge for aging mitotic cells.

Data availability

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

The following previously published data sets were used

Article and author information

Author details

  1. Irina L Rempel

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  2. Matthew M Crane

    Department of Pathology, University of Washington, Seattle, United States
    For correspondence
    nomad.crane@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6234-0954
  3. David J Thaller

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3577-5562
  4. Ankur Mishra

    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  5. Daniel PM Jansen

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  6. Georges Janssens

    European Research Institute for the Biology of Ageing, , University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  7. Petra Popken

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  8. Arman Akşit

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9053-701X
  9. Matt Kaeberlein

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    Matt Kaeberlein, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1311-3421
  10. Erik van der Giessen

    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8369-2254
  11. Anton Steen

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  12. Patrick R Onck

    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
  13. C Patrick Lusk

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4703-0533
  14. Liesbeth M Veenhoff

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    For correspondence
    l.m.veenhoff@rug.nl
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0158-4728

Funding

Netherlands Organization for Scientific Research (ALWOP.2015.053)

  • Liesbeth M Veenhoff

Netherlands Organization for Scientific Research (ECHO.711.013.008)

  • Liesbeth M Veenhoff

National Institutes of Health (NIH GM 105672)

  • C Patrick Lusk

National Institutes of Health (T32GM007223)

  • C Patrick Lusk

Ubbo Emmius Fund

  • Liesbeth M Veenhoff

University of Groningen and University Medical Center Groningen (Graduate Student Fellowship)

  • Patrick R Onck

Netherlands Organization for Scientific Research (SURFsara)

  • Patrick R Onck

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

Reviewing Editor

  1. Karsten Weis, ETH Zurich, Switzerland

Version history

  1. Received: May 3, 2019
  2. Accepted: June 2, 2019
  3. Accepted Manuscript published: June 3, 2019 (version 1)
  4. Version of Record published: June 17, 2019 (version 2)

Copyright

© 2019, Rempel 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. Irina L Rempel
  2. Matthew M Crane
  3. David J Thaller
  4. Ankur Mishra
  5. Daniel PM Jansen
  6. Georges Janssens
  7. Petra Popken
  8. Arman Akşit
  9. Matt Kaeberlein
  10. Erik van der Giessen
  11. Anton Steen
  12. Patrick R Onck
  13. C Patrick Lusk
  14. Liesbeth M Veenhoff
(2019)
Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics
eLife 8:e48186.
https://doi.org/10.7554/eLife.48186

Share this article

https://doi.org/10.7554/eLife.48186

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