Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics
Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics
复制标题
有丝分裂细胞中核孔组装的年龄依赖性退化降低了运输动力学
作者：
I. L. Rempel;Matthew M. Crane;Ankur Mishra;D. Jansen;G. Janssens;P. Popken;M. Kaeberlein;E. Giessen;P. Onck;Anton Steen;L. Veenhoff
核转运由核孔复合体（NPC）促进，并且对真核生物中的生命至关重要。NPC是一个寿命长且非常大的结构。我们询问NPC功能是否在衰老的有丝分裂细胞中受损。通过对单个酵母细胞在老化过程中的成像，我们发现几种NPC组分和NPC组装因子的丰度降低，而出现错误组装的NPC的迹象。因此，核渗透性降低，导致转录因子穿梭动力学降低和核区室化增加。在支持下降的NPC质量控制是重要的有丝分裂老化，我们发现，运输动力学观察到的老化模仿NPC组装突变体。此外，单细胞生活史表明，更好地维持NPC功能的细胞寿命更长。我们的结论是，组装和质量控制的NPC老化有丝分裂细胞的主要挑战。
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.
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