Elucidating nuclear size control in the Xenopus model system

Jevtić, Predrag; Daniel, Levy L

doi:10.2298/vetgl170731012j

Cited by 5 publications

(3 citation statements)

References 56 publications

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“…While yeast screens have been performed to identify nuclear size effectors and model systems such as Xenopus and C. elegans have begun to reveal some conserved mechanisms of nuclear size regulation , questions remain about how nuclear size is regulated in human cells. Beyond testing known mechanisms of nuclear size regulation in mammalian cells, imaging‐based RNAi screens offer an opportunity to identify novel nuclear size effectors .…”

Section: Introductionmentioning

confidence: 99%

The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity

et al. 2019

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How intracellular organelles acquire their characteristic sizes is a fundamental question in cell biology. Given stereotypical changes in nuclear size in cancer, it is important to understand the mechanisms that control nuclear size in human cells. Using a high‐throughput imaging RNAi screen, we identify and mechanistically characterize ELYS, a nucleoporin required for post‐mitotic nuclear pore complex (NPC) assembly, as a determinant of nuclear size in mammalian cells. ELYS knockdown results in small nuclei, reduced nuclear lamin B2 localization, lower NPC density, and decreased nuclear import. Increasing nuclear import by importin α overexpression rescues nuclear size and lamin B2 import, while inhibiting importin α/β‐mediated nuclear import decreases nuclear size. Conversely, ELYS overexpression increases nuclear size, enriches nuclear lamin B2 at the nuclear periphery, and elevates NPC density and nuclear import. Consistent with these observations, knockdown or inhibition of exportin 1 increases nuclear size. Thus, we identify ELYS as a novel positive effector of mammalian nuclear size and propose that nuclear size is sensitive to NPC density and nuclear import capacity.

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Section: Introductionmentioning

confidence: 99%

The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity

et al. 2019

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“…This review focuses on nuclear morphology and chromatin organization in cancer. We mainly discuss studies performed in mammalian cells and systems as many fine reviews have covered related topics in nonmammalian systems [7][8][9][10][11][12][13][14][15]. Finally, we discuss unanswered questions concerning the interplay between nuclear dynamics and chromatin structure and the impact of these processes on pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Dynamics and Chromatin Structure: Implications for Pancreatic Cancer

Flores

Tader

Tolosa

et al. 2021

Cells

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Changes in nuclear shape have been extensively associated with the dynamics and functionality of cancer cells. In most normal cells, nuclei have a regular ellipsoid shape and minimal variation in nuclear size; however, an irregular nuclear contour and abnormal nuclear size is often observed in cancer, including pancreatic cancer. Furthermore, alterations in nuclear morphology have become the ‘gold standard’ for tumor staging and grading. Beyond the utility of altered nuclear morphology as a diagnostic tool in cancer, the implications of altered nuclear structure for the biology and behavior of cancer cells are profound as changes in nuclear morphology could impact cellular responses to physical strain, adaptation during migration, chromatin organization, and gene expression. Here, we aim to highlight and discuss the factors that regulate nuclear dynamics and their implications for pancreatic cancer biology.

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“…There is growing evidence that early embryogenesis and cancer progression share similar cellular features and that many embryo-specific genes and signaling pathways are reactivated in cancer [30, 31]. For these reasons, we were particularly interested to test the developmental consequences of altering NTF2 levels because of its potential involvement in carcinogenesis [13, 32, 33]. In this study, we investigate how altering the levels of nuclear import factors in X .…”

Section: Introductionmentioning

confidence: 99%

Altering the levels of nuclear import factors in early Xenopus laevis embryos affects later development

et al. 2019

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More than just a container for DNA, the nuclear envelope carries out a wide variety of critical and highly regulated cellular functions. One of these functions is nuclear import, and in this study we investigate how altering the levels of nuclear transport factors impacts developmental progression and organismal size. During early Xenopus laevis embryogenesis, the timing of a key developmental event, the midblastula transition (MBT), is sensitive to nuclear import factor levels. How might altering nuclear import factors and MBT timing in the early embryo affect downstream development of the organism? We microinjected X . laevis two-cell embryos with mRNA to increase levels of importin α or NTF2, resulting in differential amounts of nuclear import factors in the two halves of the embryo. Compared to controls, these embryos exhibited delayed gastrulation, curved neural plates, and bent tadpoles with different sized eyes. Furthermore, embryos microinjected with NTF2 developed into smaller froglets compared to control microinjected embryos. We propose that altering nuclear import factors and nuclear size affects MBT timing, cell size, and cell number, subsequently disrupting later development. Thus, altering nuclear import factors early in development can affect function and size at the organismal level.

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Elucidating nuclear size control in the Xenopus model system

Cited by 5 publications

References 56 publications

The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity

The nucleoporin ELYS regulates nuclear size by controlling NPC number and nuclear import capacity

Nuclear Dynamics and Chromatin Structure: Implications for Pancreatic Cancer

Altering the levels of nuclear import factors in early Xenopus laevis embryos affects later development

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