Document Detail

Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins.
MedLine Citation:
PMID:  20079404     Owner:  NLM     Status:  MEDLINE    
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.
Winnok H De Vos; Frederik Houben; Ron A Hoebe; Raoul Hennekam; Baziel van Engelen; Erik M M Manders; Frans C S Ramaekers; Jos L V Broers; Patrick Van Oostveldt
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Publication Detail:
Type:  Journal Article     Date:  2010-01-14
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1800     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-08     Completed Date:  2010-06-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  448-58     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.
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MeSH Terms
Cell Line
Cell Shape
Codon, Nonsense*
Fibroblasts / pathology,  physiology*
Lamin Type A / deficiency,  genetics*
Nuclear Envelope / genetics*,  metabolism
Nuclear Proteins / genetics,  metabolism
Polymorphism, Single Nucleotide
Progeria / genetics*,  metabolism,  pathology
Protein Precursors / genetics,  metabolism
Reference Values
Skin / cytology
Skin Physiological Phenomena
Reg. No./Substance:
0/Codon, Nonsense; 0/LMNA protein, human; 0/Lamin Type A; 0/Nuclear Proteins; 0/Protein Precursors; 0/lamin C; 0/prelamin A

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