We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.
- Authors
Lammerding, Jan; Schulze, P Christian; Takahashi, Tomosaburo; Kozlov, Serguei; Sullivan, Teresa; Kamm, Roger D; Stewart, Colin L; Lee, Richard T
- Abstract
Mutations in the lamin A/C gene (LMNA) cause a variety of human diseases including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. The tissue-specific effects of lamin mutations are unclear, in part because the function of lamin A/C is incompletely defined, but the many muscle-specific phenotypes suggest that defective lamin A/C could increase cellular mechanical sensitivity. To investigate the role of lamin A/C in mechanotransduction, we subjected lamin A/C-deficient mouse embryo fibroblasts to mechanical strain and measured nuclear mechanical properties and strain-induced signaling. We found that Lmna-/- cells have increased nuclear deformation, defective mechanotransduction, and impaired viability under mechanical strain. NF-kappaB-regulated transcription in response to mechanical or cytokine stimulation was attenuated in Lmna-/- cells despite increased transcription factor binding. Lamin A/C deficiency is thus associated with both defective nuclear mechanics and impaired mechanically activated gene transcription. These findings suggest that the tissue-specific effects of lamin A/C mutations observed in the laminopathies may arise from varying degrees of impaired nuclear mechanics and transcriptional activation.
- Publication
The Journal of clinical investigation, 2004, Vol 113, Issue 3, p370
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI19670