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

Irina L Rempel, Matthew M Crane, David J Thaller, Ankur Mishra, Daniel P M Jansen, Georges Janssens, Petra Popken, Arman Akşit, Matt Kaeberlein, Erik van der Giessen, Anton Steen, Patrick R Onck, C Patrick Lusk, Liesbeth M Veenhoff

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    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 compartmentalization. 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.

    Original languageEnglish
    Article numbere48186
    Number of pages26
    JournaleLife
    Volume8
    DOIs
    Publication statusPublished - 3-Jun-2019

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