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

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

doi:10.7554/elife.48186

Irina L Rempel, Petra Popken + Show 12 more

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

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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.

Highlights

Rapid and controlled transport and communication between the nucleus and cytosol are essential for life in eukaryotes and malfunction is linked to cancer and neurodegeneration
We validated that changes in relative abundance of the Nups at the nuclear envelope were in line with the changes found in the proteome
Our data is consistent with a model where Nuclear Pore Complex (NPC) assembly and quality control are compromised in mitotic aging (Figure 2) and where misassembled NPCs, which lack the FG-Nups that we see declining in aging (Figure 1), accumulate in aged cells (Figure 3)

Summary

Introduction

Rapid and controlled transport and communication between the nucleus and cytosol are essential for life in eukaryotes and malfunction is linked to cancer and neurodegeneration (reviewed in Fichtman and Harel, 2014). The components of the symmetric core scaffold are long lived both in dividing yeast cells and in postmitotic cells, while several FG-Nups are turned over (D’Angelo et al, 2009; Denoth-Lippuner et al, 2014; Savas et al, 2012; Thayer et al, 2014; Toyama et al, 2013) and dynamically associate with the NPC (Dilworth et al, 2001; Nino et al, 2016; Rabut et al, 2004). Previous studies performed in postmitotic aging cells (chronological aging) showed changes in NPC structure and function (D’Angelo et al, 2009; Toyama et al, 2019), and in aging mitotic cells (replicative aging) changes in NPCs have been described

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