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

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

doi:10.7554/elife.48186

Cited by 69 publications

(96 citation statements)

References 86 publications

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“…However, a recent study performed in yeast concluded that oxidative damage is unlikely to be a direct cause for the age‐dependent deterioration of nuclear transport. Alternatively, Rempel et al (2019) proposed that in aged cells, misassembled NPCs accumulate as a result of NPC assembly quality control decline leading to a reduction of permeable and functional NPCs, and a consequent decrease in the transport dynamics (Rempel et al, 2019).…”

Section: Nuclear Transportmentioning

confidence: 99%

Nuclear envelope dysfunction and its contribution to the aging process

et al. 2020

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The nuclear envelope (NE) is the central organizing unit of the eukaryotic cell serving as a genome protective barrier and mechanotransduction interface between the cytoplasm and the nucleus. The NE is mainly composed of a nuclear lamina and a double membrane connected at specific points where the nuclear pore complexes (NPCs) form. Physiological aging might be generically defined as a functional decline across lifespan observed from the cellular to organismal level. Therefore, during aging and premature aging, several cellular alterations occur, including nuclear‐specific changes, particularly, altered nuclear transport, increased genomic instability induced by DNA damage, and telomere attrition. Here, we highlight and discuss proteins associated with nuclear transport dysfunction induced by aging, particularly nucleoporins, nuclear transport factors, and lamins. Moreover, changes in the structure of chromatin and consequent heterochromatin rearrangement upon aging are discussed. These alterations correlate with NE dysfunction, particularly lamins’ alterations. Finally, telomere attrition is addressed and correlated with altered levels of nuclear lamins and nuclear lamina‐associated proteins. Overall, the identification of molecular mechanisms underlying NE dysfunction, including upstream and downstream events, which have yet to be unraveled, will be determinant not only to our understanding of several pathologies, but as here discussed, in the aging process.

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Section: Nuclear Transportmentioning

confidence: 99%

Nuclear envelope dysfunction and its contribution to the aging process

et al. 2020

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“…In dividing cells, NPCs disassemble during mitosis and rearrange afterwards in the newly formed cells (180). Rempel et al showed that NPC quality control is compromised in aging mitotic cells, which results in decreased NPC function and impaired transcription factor shuttling (181). The maintenance of NPCs in long-lived post-mitotic cells, such as neurons, is provided through the renewal of individual NPC subcomplexes, whereby scaffold Nups remain assembled and installed in the NPC during the entire cellular life span (144,182).…”

Section: Nct Impairments In Normal Agingmentioning

confidence: 99%

Nuclear Transport Deficits in Tau-Related Neurodegenerative Diseases

Diez

Wegmann

2020

Front. Neurol.

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Tau is a cytosolic microtubule binding protein that is highly abundant in the axons of the central nervous system. However, alternative functions of tau also in other cellular compartments are suggested, for example, in the nucleus, where interactions of tau with specific nuclear entities such as DNA, the nucleolus, and the nuclear envelope have been reported. We would like to review the current knowledge about tau-nucleus interactions and lay out possible neurotoxic mechanisms that are based on the (pathological) interactions of tau with the nucleus.

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“…The assembly of new NPCs is complex and heavily dependent on the presence of the proper amounts of NPC components and assembly factors. Altogether, the biochemical properties of NPCs set them at risk for age‐related decline and, indeed, several studies addressed age‐related changes of the NPC, and/or nucleocytoplasmic transport in aging .…”

Section: Introductionmentioning

confidence: 99%

Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging

2020

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The nuclear pore complex (NPC) is the sole gateway to the nuclear interior, and its function is essential to all eukaryotic life. Controlling the functionality of NPCs is a tremendous challenge for cells. Firstly, NPCs are large structures, and their complex assembly does occasionally go awry. Secondly, once assembled, some components of the NPC persist for an extremely long time and, as a result, are susceptible to accumulate damage. Lastly, a significant proportion of the NPC is composed of intrinsically disordered proteins that are prone to aggregation. In this review, we summarize how the quality of NPCs is guarded in young cells and discuss the current knowledge on the fate of NPCs during normal aging in different tissues and organisms. We discuss the extent to which current data supports a hypothesis that NPCs are poorly maintained during aging of nondividing cells, while in dividing cells the main challenge is related to the assembly of new NPCs. Our survey of current knowledge points toward NPC quality control as an important node in aging of both dividing and nondividing cells. Here, the loss of protein homeostasis during aging is central and the NPC appears to both be impacted by, and to drive, this process.

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

Cited by 69 publications

References 86 publications

Nuclear envelope dysfunction and its contribution to the aging process

Nuclear envelope dysfunction and its contribution to the aging process

Nuclear Transport Deficits in Tau-Related Neurodegenerative Diseases

Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging

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