Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics
- University of Groningen, Netherlands
- University of Washington, United States
- Yale School of Medicine, United States
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.
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Yeast transcriptome profiling in replicative ageingArrayExpress, E-MTAB-3605.
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Aging YeastEMBL-EBI PRIDE Archive, PXD001714.
Article and author information
Author details
Erik van der Giessen
Liesbeth M Veenhoff
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
- Karsten Weis, ETH Zurich, Switzerland
Publication history
- Received: May 3, 2019
- Accepted: June 2, 2019
- Accepted Manuscript published: June 3, 2019 (version 1)
- 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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Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics
eLife 8:e48186.
https://doi.org/10.7554/eLife.48186
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