Document Detail

Disturbed nuclear orientation and cellular migration in A-type lamin deficient cells.
MedLine Citation:
PMID:  19013199     Owner:  NLM     Status:  MEDLINE    
The nuclear lamina and the cytoskeleton form an integrated structure that warrants proper mechanical functioning of cells. We have studied the correlation between structural alterations and migrational behaviour in fibroblasts with and without A-type lamins. We show that loss of A-type lamins causes loss of emerin and nesprin-3 from the nuclear envelope, concurring with a disturbance in the connection between the nucleus and the cytoskeleton in A-type lamin-deficient (lmna -/-) cells. In these cells functional migration assays during in vitro wound healing revealed a delayed reorientation of the nucleus and the microtubule-organizing center during migration, as well as a loss of nuclear oscillatory rotation. These observations in fibroblasts isolated from lmna knockout mice were confirmed in a 3T3 cell line with stable reduction of lmna expression due to RNAi approach. Our results indicate that A-type lamins play a key role in maintaining directional movement governed by the cytoskeleton, and that the loss of these karyoskeletal proteins has important consequences for functioning of the cell as a mechanical entity.
F Houben; C H M P Willems; I L J Declercq; K Hochstenbach; M A Kamps; L H E H Snoeckx; F C S Ramaekers; J L V Broers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-25
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1793     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-26     Completed Date:  2009-04-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  312-24     Citation Subset:  IM    
Department of Molecular Cell Biology (Box 17), School for Cardiovascular Diseases (CARIM), Maastricht University, P.O. Box 616, NL-6200 MD Maastricht, The Netherlands.
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MeSH Terms
3T3 Cells
Biological Assay
Cell Movement*
Cell Nucleus / metabolism*
Cell Polarity*
Fibroblasts / cytology*,  metabolism
Lamin Type A / deficiency*,  metabolism
Membrane Proteins / metabolism
Microtubule-Organizing Center / metabolism
Nuclear Proteins / metabolism
Protein Transport
RNA Interference
Wound Healing
Reg. No./Substance:
0/Lamin Type A; 0/Membrane Proteins; 0/Nuclear Proteins; 0/nesprin-3 protein, mouse

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