Cargando…

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.,...

Descripción completa

Detalles Bibliográficos
Autores principales: Lammerding, Jan, Hsiao, Janet, Schulze, P. Christian, Kozlov, Serguei, Stewart, Colin L., Lee, Richard T.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171355/
https://www.ncbi.nlm.nih.gov/pubmed/16115958
http://dx.doi.org/10.1083/jcb.200502148
_version_ 1782144923103920128
author Lammerding, Jan
Hsiao, Janet
Schulze, P. Christian
Kozlov, Serguei
Stewart, Colin L.
Lee, Richard T.
author_facet Lammerding, Jan
Hsiao, Janet
Schulze, P. Christian
Kozlov, Serguei
Stewart, Colin L.
Lee, Richard T.
author_sort Lammerding, Jan
collection PubMed
description 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.
format Text
id pubmed-2171355
institution National Center for Biotechnology Information
language English
publishDate 2005
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21713552008-03-05 Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells Lammerding, Jan Hsiao, Janet Schulze, P. Christian Kozlov, Serguei Stewart, Colin L. Lee, Richard T. J Cell Biol Research Articles 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. The Rockefeller University Press 2005-08-29 /pmc/articles/PMC2171355/ /pubmed/16115958 http://dx.doi.org/10.1083/jcb.200502148 Text en Copyright © 2005, Government This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Lammerding, Jan
Hsiao, Janet
Schulze, P. Christian
Kozlov, Serguei
Stewart, Colin L.
Lee, Richard T.
Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
title Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
title_full Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
title_fullStr Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
title_full_unstemmed Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
title_short Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
title_sort abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171355/
https://www.ncbi.nlm.nih.gov/pubmed/16115958
http://dx.doi.org/10.1083/jcb.200502148
work_keys_str_mv AT lammerdingjan abnormalnuclearshapeandimpairedmechanotransductioninemerindeficientcells
AT hsiaojanet abnormalnuclearshapeandimpairedmechanotransductioninemerindeficientcells
AT schulzepchristian abnormalnuclearshapeandimpairedmechanotransductioninemerindeficientcells
AT kozlovserguei abnormalnuclearshapeandimpairedmechanotransductioninemerindeficientcells
AT stewartcolinl abnormalnuclearshapeandimpairedmechanotransductioninemerindeficientcells
AT leerichardt abnormalnuclearshapeandimpairedmechanotransductioninemerindeficientcells