title: Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells.
abstract: 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.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. jlammerding@rics.bwh.harvard.edu
authors.forename: Jan
authors.initials: J
authors.lastname: Lammerding
authors.forename: Janet
authors.initials: J
authors.lastname: Hsiao
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
authors.forename: Serguei
authors.initials: S
authors.lastname: Kozlov
authors.forename: Colin L
authors.initials: CL
authors.lastname: Stewart
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D013946:Thymopoietins / Q000235:genetics / Q000378:metabolism*
chemical_list: D034904:Lamin Type A; D008565:Membrane Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin