RT Journal Article
SR Electronic
T1 Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 477802
DO 10.1101/477802
A1 I.L. Rempel
A1 M.M. Crane
A1 A. Mishra
A1 D.P.M. Jansen
A1 G.E. Janssens
A1 P. Popken
A1 M. Kaeberlein
A1 E. Van der Giessen
A1 P.R. Onck
A1 A. Steen
A1 L.M. Veenhoff
YR 2018
UL http://biorxiv.org/content/early/2018/11/24/477802.abstract
AB 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 function is compromised in ageing mitotic cells. By imaging of single yeast cells during ageing, we show that the abundance of several NPC components and NPC assembly factors decreases while signs of misassembled NPCs appear. Consequently, nuclear permeability decreases, resulting in decreased dynamics of transcription factor shuttling and increased nuclear compartmentalisation. In support that declining NPC quality control is important in mitotic ageing, we find that the transport kinetics observed in ageing is mimicked in an NPC assembly mutant. Additionally, the single cell life histories reveal that cells that better maintain NPC function are longer lived. We conclude that assembly and quality control of NPCs are major challenges for ageing mitotic cells.