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Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies

(2011) HUMAN MOLECULAR GENETICS. 20(21). p.4175-4186
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Abstract
The nuclear lamina provides structural support to the nucleus and has a central role in nuclear organization and gene regulation. Defects in its constituents, the lamins, lead to a class of genetic diseases collectively referred to as laminopathies. Using live cell imaging, we observed the occurrence of intermittent, non-lethal ruptures of the nuclear envelope in dermal fibroblast cultures of patients with different mutations of lamin A/C. These ruptures, which were absent in normal fibroblasts, could be mimicked by selective knockdown as well as knockout of LMNA and were accompanied by the loss of cellular compartmentalization. This was demonstrated by the influx of cytoplasmic transcription factor RelA and regulatory protein Cyclin B1 into the nucleus, and efflux of nuclear transcription factor OCT1 and nuclear structures containing the promyelocytic leukemia (PML) tumour suppressor protein to the cytoplasm. While recovery of enhanced yellow fluorescent protein-tagged nuclear localization signal in the nucleus demonstrated restoration of nuclear membrane integrity, part of the mobile PML structures became permanently translocated to the cytoplasm. These satellite PML structures were devoid of the typical PML body components, such as DAXX, SP100 or SUMO1. Our data suggest that nuclear rupture and loss of compartmentalization may add to cellular dysfunction and disease development in various laminopathies.
Keywords
LMNA GENE MUTATION, GILFORD-PROGERIA-SYNDROME, A-TYPE LAMINS, TRANSCRIPTION FACTOR, COMPOUND HETEROZYGOSITY, MUSCULAR-DYSTROPHY, OXIDATIVE STRESS, PROTEIN IMPORT, CELLS, DISEASE

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Citation

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Chicago
De Vos, Winnok, Frederik Houben, Miriam Kamps, Ashraf Malhas, Fons Verheyen, Juliën Cox, Erik Manders, et al. 2011. “Repetitive Disruptions of the Nuclear Envelope Invoke Temporary Loss of Cellular Compartmentalization in Laminopathies.” Human Molecular Genetics 20 (21): 4175–4186.
APA
De Vos, Winnok, Houben, F., Kamps, M., Malhas, A., Verheyen, F., Cox, J., Manders, E., et al. (2011). Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies. HUMAN MOLECULAR GENETICS, 20(21), 4175–4186.
Vancouver
1.
De Vos W, Houben F, Kamps M, Malhas A, Verheyen F, Cox J, et al. Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies. HUMAN MOLECULAR GENETICS. 2011;20(21):4175–86.
MLA
De Vos, Winnok, Frederik Houben, Miriam Kamps, et al. “Repetitive Disruptions of the Nuclear Envelope Invoke Temporary Loss of Cellular Compartmentalization in Laminopathies.” HUMAN MOLECULAR GENETICS 20.21 (2011): 4175–4186. Print.
@article{1888640,
  abstract     = {The nuclear lamina provides structural support to the nucleus and has a central role in nuclear organization and gene regulation. Defects in its constituents, the lamins, lead to a class of genetic diseases collectively referred to as laminopathies. Using live cell imaging, we observed the occurrence of intermittent, non-lethal ruptures of the nuclear envelope in dermal fibroblast cultures of patients with different mutations of lamin A/C. These ruptures, which were absent in normal fibroblasts, could be mimicked by selective knockdown as well as knockout of LMNA and were accompanied by the loss of cellular compartmentalization. This was demonstrated by the influx of cytoplasmic transcription factor RelA and regulatory protein Cyclin B1 into the nucleus, and efflux of nuclear transcription factor OCT1 and nuclear structures containing the promyelocytic leukemia (PML) tumour suppressor protein to the cytoplasm. While recovery of enhanced yellow fluorescent protein-tagged nuclear localization signal in the nucleus demonstrated restoration of nuclear membrane integrity, part of the mobile PML structures became permanently translocated to the cytoplasm. These satellite PML structures were devoid of the typical PML body components, such as DAXX, SP100 or SUMO1. Our data suggest that nuclear rupture and loss of compartmentalization may add to cellular dysfunction and disease development in various laminopathies.},
  author       = {De Vos, Winnok and Houben, Frederik and Kamps, Miriam and Malhas, Ashraf and Verheyen, Fons and Cox, Juli{\"e}n and Manders, Erik and Verstraeten, Valerie LRM and van Steensel, Maurice AM and Marcelis, Carlo LM and van den Wijngaard, Arthur and Vaux, David J and Ramaekers, Frans CS and Broers, Jos LV},
  issn         = {0964-6906},
  journal      = {HUMAN MOLECULAR GENETICS},
  keyword      = {LMNA GENE MUTATION,GILFORD-PROGERIA-SYNDROME,A-TYPE LAMINS,TRANSCRIPTION FACTOR,COMPOUND HETEROZYGOSITY,MUSCULAR-DYSTROPHY,OXIDATIVE STRESS,PROTEIN IMPORT,CELLS,DISEASE},
  language     = {eng},
  number       = {21},
  pages        = {4175--4186},
  title        = {Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies},
  url          = {http://dx.doi.org/10.1093/hmg/ddr344},
  volume       = {20},
  year         = {2011},
}

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