Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. We recently demonstrated that A-type lamin-deficient cells have impaired nuclear mechanics and altered mechanotransduction, suggesting two potential disease mechanisms (Lammerding, J.,...
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Published in | The Journal of cell biology Vol. 170; no. 5; pp. 781 - 791 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Rockefeller University Press
29.08.2005
The Rockefeller University Press |
Subjects | |
Online Access | Get full text |
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Summary: | Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. We recently demonstrated that A-type lamin-deficient cells have impaired nuclear mechanics and altered mechanotransduction, suggesting two potential disease mechanisms (Lammerding, J., P.C. Schulze, T. Takahashi, S. Kozlov, T. Sullivan, R.D. Kamm, C.L. Stewart, and R.T. Lee. 2004. J. Clin. Invest. 113:370-378). Here, we examined the function of emerin on nuclear mechanics and strain-induced signaling. Emerin-deficient mouse embryo fibroblasts have abnormal nuclear shape, but in contrast to A-type lamin-deficient cells, exhibit nuclear deformations comparable to wild-type cells in cellular strain experiments, and the integrity of emerin-deficient nuclear envelopes appeared normal in a nuclear microinjection assay. Interestingly, expression of mechanosensitive genes in response to mechanical strain was impaired in emerin-deficient cells, and prolonged mechanical stimulation increased apoptosis in emerin-deficient cells. Thus, emerin-deficient mouse embryo fibroblasts have apparently normal nuclear mechanics but impaired expression of mechanosensitive genes in response to strain, suggesting that emerin mutations may act through altered transcriptional regulation and not by increasing nuclear fragility. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Abbreviations used in this paper: BAF, barrier-to-autointegration factor; EDMD, Emery-Dreifuss muscular dystrophy; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GCL, germ cell-less. Correspondence to Jan Lammerding: jlammerding@rics.bwh.harvard.edu |
ISSN: | 0021-9525 1540-8140 |
DOI: | 10.1083/jcb.200502148 |