A systematic genomic screen implicates nucleocytoplasmic transport and membrane growth in nuclear size control

Kume, Kazunori; Cantwell, Helena; Neumann, Frank; Jones, Andrew W.; Snijders, Ambrosius P.; Nurse, Paul

doi:10.1371/journal.pgen.1006767

Cited by 65 publications

(96 citation statements)

References 43 publications

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“…In budding yeast, nuclear size expands with cell growth and does not directly depend on DNA content (Jorgensen et al, 2007). These studies conclude that, counter to the nucleoskeletal theory, nuclear size depends largely on cytoplasmic volume (Jorgensen et al, 2007;Kume et al, 2017).…”

Section: Distinctions Between Endopolyploidy and Wgm Ploidy Changementioning

confidence: 70%

Ploidy and Size at Multiple Scales in the Arabidopsis Sepal

et al. 2018

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Ploidy and size phenomena are observed to be correlated across several biological scales, from subcellular to organismal. Two kinds of ploidy change can affect plants. Whole-genome multiplication increases ploidy in whole plants and is broadly associated with increases in cell and organism size. Endoreduplication increases ploidy in individual cells. Ploidy increase is strongly correlated with increased cell size and nuclear volume. Here, we investigate scaling relationships between ploidy and size by simultaneously quantifying nuclear size, cell size, and organ size in sepals from an isogenic series of diploid, tetraploid, and octoploid Arabidopsis thaliana plants, each of which contains an internal endopolyploidy series. We find that pavement cell size and transcriptome size increase linearly with whole-organism ploidy, but organ area increases more modestly due to a compensatory decrease in cell number. We observe that cell size and nuclear size are maintained at a constant ratio; the value of this constant is similar in diploid and tetraploid plants and slightly lower in octoploid plants. However, cell size is maintained in a mutant with reduced nuclear size, indicating that cell size is scaled to cell ploidy rather than to nuclear size. These results shed light on how size is regulated in plants and how cells and organisms of differing sizes are generated by ploidy change.

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Section: Distinctions Between Endopolyploidy and Wgm Ploidy Changementioning

confidence: 70%

Ploidy and Size at Multiple Scales in the Arabidopsis Sepal

et al. 2018

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“…Increases in nuclear size can be driven by increased chromosome numbers or impaired transport of mRNA or proteins out of the nucleus 22 . In these novel TMZ resistant models, we hypothesized that the increase in nuclear size was a function of retained chromosomes.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Tiek

Rone

Graham

et al. 2017

Preprint

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Glioblastoma (GBM) is an aggressive and incurable tumor of the brain with limited treatment options. Current first-line standard of care is the DNA alkylating agent temozolomide (TMZ), but this treatment strategy adds only ~4 months to median survival due to the rapid development of resistance. While some mechanisms of TMZ resistance have been identified, they are not fully understood. There are few effective strategies to manage therapy resistant GBM, and we lack diverse preclinical models of acquired TMZ resistance in which to test therapeutic strategies on TMZ resistant GBM. In this study, we create and characterize two new GBM cell lines resistant to TMZ, based on the 8MGBA and 42MGBA cell lines. Analysis of the TMZ resistant (TMZres) variants in conjunction with their parental, sensitive cell lines shows that acquisition of TMZ resistance is accompanied by broad phenotypic changes, including increased proliferation, migration, chromosomal aberrations and secretion of cytosolic lipids. Importantly, each TMZ resistant model captures a different facet of the "go" (8MGBA-TMZres) or "grow" (42MGBA-TMZres) hypothesis of GBM behavior. These model systems will be important additions to the available tools for investigators seeking to define molecular mechanisms of acquired TMZ resistance.. CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a

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“…Thus, changes in the expression and/or localization of importin α, lamins, and PKC all contribute to developmental nuclear size-scaling in Xenopus. Similar factors and mechanisms influence nuclear size in yeast, C. elegans, D. melanogaster, T. thermophila, and cultured human cells (Brandt et al, 2006;Jevtic and Levy, 2014;Kume et al, 2017;Ladouceur et al, 2015;Liu et al, 2000;Malone et al, 2008;Meyerzon et al, 2009;Neumann and Nurse, 2007;Vukovic et al, 2016a;Vukovic et al, 2016b), showing that Xenopus development can inform conserved mechanisms of nuclear size control.…”

Section: Introductionmentioning

confidence: 98%

Cytoplasmic volume and limiting nucleoplasmin scale nuclear size duringXenopus laevisdevelopment

Chen

Tomschik

Nelson

et al. 2019

Preprint

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How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size-scaling factor. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. Thus, reductions in cell volume with concomitant decreases in Npm2 amounts represent a developmental mechanism of nuclear size-scaling that may also be relevant to cancers with increased nuclear size.

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A systematic genomic screen implicates nucleocytoplasmic transport and membrane growth in nuclear size control

Cited by 65 publications

References 43 publications

Ploidy and Size at Multiple Scales in the Arabidopsis Sepal

Ploidy and Size at Multiple Scales in the Arabidopsis Sepal

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Cytoplasmic volume and limiting nucleoplasmin scale nuclear size duringXenopus laevisdevelopment

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