Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells

• Published in: The Journal of cell biology Vol. 170; no. 5; pp. 781 - 791
• Main Authors: Lammerding, Jan, Hsiao, Janet, Schulze, P. Christian, Kozlov, Serguei, Stewart, Colin L, Lee, Richard T
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 29.08.2005; The Rockefeller University Press
• Subjects: Animals; Apoptosis; Cell lines; Cell nucleus; Cell Nucleus - metabolism; Cell Nucleus - ultrastructure; Cells; Cells, Cultured; Cellular biology; Embryos; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Fracture mechanics; Humans; Lamin Type A - genetics; Lamin Type A - metabolism; Lamins; Mechanotransduction, Cellular - physiology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Knockout; Muscular Dystrophy, Emery-Dreifuss - genetics; Muscular Dystrophy, Emery-Dreifuss - metabolism; Mutation; NF-kappa B - metabolism; Nuclear membrane; Nuclear Proteins; Proteins; Signal transduction; Signal Transduction - physiology; Space life sciences; Stress, Mechanical; Structural strain; Thymopoietins - genetics; Thymopoietins - metabolism; Non-programmatic
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200502148

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.