Nuclear envelope rupture is induced by actin-based nucleus confinement

Hatch, Emily M.; Hetzer, Martin W.

doi:10.1083/jcb.201603053

Cited by 240 publications

(334 citation statements)

References 39 publications

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“…1) that precede NE rupture and that collapse upon nuclear membrane rupture [6][7][8][9][10][11] suggest that these events are driven by an increase in intranuclear pressure due to forces, possibly generated by the cytoskeleton, that compress the nucleus. Notably, even nuclei in unconfined cells cultured on 2D substrates experience compressive forces from the contractile actomyosin filaments spanning the nucleus.…”

Section: 11mentioning

confidence: 99%

“…Notably, even nuclei in unconfined cells cultured on 2D substrates experience compressive forces from the contractile actomyosin filaments spanning the nucleus. 8 Supporting a role for the cytoskeleton, treatment with either the myosin inhibitor blebbistatin or the actin polymerization inhibitor cytochalasin, which reduces the tension of the actin cytoskeleton, also reduces the NE rupture rates. 8,10 In contrast, when cytochalasin D treated cells are subjected to external vertical confinement to match nuclear compression levels of untreated cells, their NE rupture rate rises to that of unconfined cells.…”

Section: 11mentioning

confidence: 99%

“…8 Supporting a role for the cytoskeleton, treatment with either the myosin inhibitor blebbistatin or the actin polymerization inhibitor cytochalasin, which reduces the tension of the actin cytoskeleton, also reduces the NE rupture rates. 8,10 In contrast, when cytochalasin D treated cells are subjected to external vertical confinement to match nuclear compression levels of untreated cells, their NE rupture rate rises to that of unconfined cells. This finding is consistent with a model in which NE bleb formation-and subsequently rupture-arise from intranuclear pressure, rather than from local cytoskeletal pulling on nuclear membrane segments.…”

Section: 11mentioning

confidence: 99%

“…This finding is consistent with a model in which NE bleb formation-and subsequently rupture-arise from intranuclear pressure, rather than from local cytoskeletal pulling on nuclear membrane segments. 8 During confined migration, the nuclear membrane bulges out and blebs at sites of defects in the nuclear lamina. 7,10 It remains unclear whether these nuclear lamina defects, which precede nuclear membrane bleb formation, are caused by excessive nuclear deformation during migration or are pre-existing abnormalities in the nuclear envelope.…”

Section: 11mentioning

confidence: 99%

“…1). [6][7][8][9][10][11] NE ruptures can also be detected by monitoring fluorescent proteins tagged with a nuclear export signal (NES), which only enter the nucleus during NE rupture and are exported back into the cytoplasm once NE integrity is restored. 6,10 In addition to these fluorescent reporters, evidence of NE rupture comes from mitochondria and ribosomes that become mislocalized to the nucleus, and promyelocytic leukemia (PML) nuclear bodies found in the cytoplasm of cells that exhibited NE rupture.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Consequences of a tight squeeze: Nuclear envelope rupture and repair

Isermann

Lammerding

2017

Nucleus

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Cell migration through tight spaces can induce substantial deformations of the nucleus and cause nuclear envelope (NE) rupture, resulting in uncontrolled exchange of nuclear and cytosolic proteins. These events can cause DNA damage and, in severe cases, nuclear fragmentation, challenging the integrity of the genomic material. Cells overcome NE ruptures during interphase by repairing the NE using components of the endosomal sorting complexes required for transport (ESCRT) machinery. Paralleling the molecular mechanism used during NE reformation in late mitosis, ESCRT-III subunits and the associated AAA-ATPase VPS4B are recruited to NE rupture sites and help restore NE integrity. While these findings are common to many cell types, they are particularly relevant in the context of cancer metastasis, where nuclear deformation and rupture could drive genomic instability in invading cells and further promote cancer progression. At the same time, inhibiting NE repair may offer new therapeutic approaches to specifically target invasive cancer cells.

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Section: 11mentioning

confidence: 99%

Section: 11mentioning

confidence: 99%

Section: 11mentioning

confidence: 99%

Section: 11mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Consequences of a tight squeeze: Nuclear envelope rupture and repair

Isermann

Lammerding

2017

Nucleus

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Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration

Cristi,

Rapuri,

Coyne

2023

FEBS Letters

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Nuclear pore complexes (NPCs) play a critical role in maintaining the equilibrium between the nucleus and cytoplasm, enabling bidirectional transport across the nuclear envelope, and are essential for proper nuclear organization and gene regulation. Perturbations in the regulatory mechanisms governing NPCs and nuclear envelope homeostasis have been implicated in the pathogenesis of several neurodegenerative diseases. The ESCRT‐III pathway emerges as a critical player in the surveillance and preservation of well‐assembled, functional NPCs, as well as nuclear envelope sealing. Recent studies have provided insights into the involvement of nuclear ESCRT‐III in the selective reduction of specific nucleoporins associated with neurodegenerative pathologies. Thus, maintaining quality control of the nuclear envelope and NPCs represents a pivotal element in the pathological cascade leading to neurodegenerative diseases. This review describes the constituents of the nuclear‐cytoplasmic transport machinery, encompassing the nuclear envelope, NPC, and ESCRT proteins, and how their structural and functional alterations contribute to the development of neurodegenerative diseases.

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Role of the Nucleus as a Sensor of Cell Environment Topography

Anselme

Wakhloo

Rougerie

et al. 2017

Adv Healthcare Materials

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The proper integration of biophysical cues from the cell vicinity is crucial for cells to maintain homeostasis, cooperate with other cells within the tissues, and properly fulfill their biological function. It is therefore crucial to fully understand how cells integrate these extracellular signals for tissue engineering and regenerative medicine. Topography has emerged as a prominent component of the cellular microenvironment that has pleiotropic effects on cell behavior. This progress report focuses on the recent advances in the understanding of the topography sensing mechanism with a special emphasis on the role of the nucleus. Here, recent techniques developed for monitoring the nuclear mechanics are reviewed and the impact of various topographies and their consequences on nuclear organization, gene regulation, and stem cell fate is summarized. The role of the cell nucleus as a sensor of cell-scale topography is further discussed.

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Nuclear envelope rupture is induced by actin-based nucleus confinement

Abstract: Hatch and Hetzer show that nuclear envelope rupture in cancer cells is caused by defects in lamina organization, resulting in an increase in intranuclear pressure from actin-based nucleus confinement.

Cited by 240 publications

References 39 publications

Consequences of a tight squeeze: Nuclear envelope rupture and repair

Consequences of a tight squeeze: Nuclear envelope rupture and repair

Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration

Role of the Nucleus as a Sensor of Cell Environment Topography

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