Ross, JA;
Levy, Y;
Ripolone, M;
Kolb, JS;
Turmaine, M;
Holt, M;
Lindqvist, J;
... Ochala, J; + view all
(2019)
Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy.
Acta Neuropathologica
, 138
(3)
pp. 477-495.
10.1007/s00401-019-02034-8.
Preview |
Text
Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy.pdf - Published Version Download (10MB) | Preview |
Abstract
Nemaline myopathy (NM) is a skeletal muscle disorder caused by mutations in genes that are generally involved in muscle contraction, in particular those related to the structure and/or regulation of the thin filament. Many pathogenic aspects of this disease remain largely unclear. Here, we report novel pathological defects in skeletal muscle fibres of mouse models and patients with NM: irregular spacing and morphology of nuclei; disrupted nuclear envelope; altered chromatin arrangement; and disorganisation of the cortical cytoskeleton. Impairments in contractility are the primary cause of these nuclear defects. We also establish the role of microtubule organisation in determining nuclear morphology, a phenomenon which is likely to contribute to nuclear alterations in this disease. Our results overlap with findings in diseases caused directly by mutations in nuclear envelope or cytoskeletal proteins. Given the important role of nuclear shape and envelope in regulating gene expression, and the cytoskeleton in maintaining muscle fibre integrity, our findings are likely to explain some of the hallmarks of NM, including contractile filament disarray, altered mechanical properties and broad transcriptional alterations.
| Type: | Article |
|---|---|
| Title: | Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00401-019-02034-8 |
| Publisher version: | https://doi.org/10.1007/s00401-019-02034-8 |
| Language: | English |
| Additional information: | © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Actin, Lamin, Microtubules, Nemaline myopathy, Nuclear envelope, Skeletal muscle |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10089880 |
Archive Staff Only
 |
View Item |
