Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins

Biochim Biophys Acta. 2010 Apr;1800(4):448-58. doi: 10.1016/j.bbagen.2010.01.002. Epub 2010 Jan 14.


Background: The nuclear lamina provides structural support to the nucleus and has a central role in defining nuclear organization. Defects in its filamentous constituents, the lamins, lead to a class of diseases collectively referred to as laminopathies. On the cellular level, lamin mutations affect the physical integrity of nuclei and nucleo-cytoskeletal interactions, resulting in increased susceptibility to mechanical stress and altered gene expression.

Methods: In this study we quantitatively compared nuclear deformation and chromatin mobility in fibroblasts from a homozygous nonsense LMNA mutation patient and a Hutchinson-Gilford progeria syndrome patient with wild type dermal fibroblasts, based on the visualization of mCitrine labeled telomere-binding protein TRF2 with light-economical imaging techniques and cytometric analyses.

Results: Without application of external forces, we found that the absence of functional lamin A/C leads to increased nuclear plasticity on the hour and minute time scale but also to increased intranuclear mobility down to the second time scale. In contrast, progeria cells show overall reduced nuclear dynamics. Experimental manipulation (farnesyltransferase inhibition or lamin A/C silencing) confirmed that these changes in mobility are caused by abnormal or reduced lamin A/C expression.

Conclusions: These observations demonstrate that A-type lamins affect both nuclear membrane and telomere dynamics.

General significance: Because of the pivotal role of dynamics in nuclear function, these differences likely contribute to or represent novel mechanisms in laminopathy development.

MeSH terms

  • Cell Line
  • Cell Shape
  • Codon, Nonsense*
  • Fibroblasts / pathology
  • Fibroblasts / physiology*
  • Humans
  • Immunohistochemistry
  • Lamin Type A / deficiency
  • Lamin Type A / genetics*
  • Nuclear Envelope / genetics*
  • Nuclear Envelope / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Polymorphism, Single Nucleotide
  • Progeria / genetics*
  • Progeria / metabolism
  • Progeria / pathology
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Reference Values
  • Skin / cytology
  • Skin Physiological Phenomena


  • Codon, Nonsense
  • LMNA protein, human
  • Lamin Type A
  • Nuclear Proteins
  • Protein Precursors
  • lamin C
  • prelamin A