Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Ross, JA, Levy, Y, Ripolone, M, Kolb, JS, Turmaine, M, Holt, M, Lindqvist, J, Claeys, KG, Weis, J, Monforte, M, Tasca, G, Moggio, M, Figeac, N, Zammit, PS, Jungbluth, H, Fiorillo, C, Vissing, J, Witting, N, Granzier, H, Zanoteli, E, Hardeman, EC, Wallgren-Pettersson, C & Ochala, J 2019, 'Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy' Acta Neuropathologica, vol. 138, no. 3, pp. 477-495. https://doi.org/10.1007/s00401-019-02034-8

APA

Ross, J. A., Levy, Y., Ripolone, M., Kolb, J. S., Turmaine, M., Holt, M., ... Ochala, J. (2019). Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy. Acta Neuropathologica, 138(3), 477-495. https://doi.org/10.1007/s00401-019-02034-8

CBE

Ross JA, Levy Y, Ripolone M, Kolb JS, Turmaine M, Holt M, Lindqvist J, Claeys KG, Weis J, Monforte M, Tasca G, Moggio M, Figeac N, Zammit PS, Jungbluth H, Fiorillo C, Vissing J, Witting N, Granzier H, Zanoteli E, Hardeman EC, Wallgren-Pettersson C, Ochala J. 2019. Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy. Acta Neuropathologica. 138(3):477-495. https://doi.org/10.1007/s00401-019-02034-8

MLA

Vancouver

Author

Ross, Jacob A ; Levy, Yotam ; Ripolone, Michela ; Kolb, Justin S ; Turmaine, Mark ; Holt, Mark ; Lindqvist, Johan ; Claeys, Kristl G ; Weis, Joachim ; Monforte, Mauro ; Tasca, Giorgio ; Moggio, Maurizio ; Figeac, Nicolas ; Zammit, Peter S ; Jungbluth, Heinz ; Fiorillo, Chiara ; Vissing, John ; Witting, Nanna ; Granzier, Henk ; Zanoteli, Edmar ; Hardeman, Edna C ; Wallgren-Pettersson, Carina ; Ochala, Julien. / Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy. In: Acta Neuropathologica. 2019 ; Vol. 138, No. 3. pp. 477-495.

Bibtex

@article{8461fb0241bc4767a3ab95ac0f4ea5c4,
title = "Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy",
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.",
author = "Ross, {Jacob A} and Yotam Levy and Michela Ripolone and Kolb, {Justin S} and Mark Turmaine and Mark Holt and Johan Lindqvist and Claeys, {Kristl G} and Joachim Weis and Mauro Monforte and Giorgio Tasca and Maurizio Moggio and Nicolas Figeac and Zammit, {Peter S} and Heinz Jungbluth and Chiara Fiorillo and John Vissing and Nanna Witting and Henk Granzier and Edmar Zanoteli and Hardeman, {Edna C} and Carina Wallgren-Pettersson and Julien Ochala",
year = "2019",
month = "9",
doi = "10.1007/s00401-019-02034-8",
language = "English",
volume = "138",
pages = "477--495",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy

AU - Ross, Jacob A

AU - Levy, Yotam

AU - Ripolone, Michela

AU - Kolb, Justin S

AU - Turmaine, Mark

AU - Holt, Mark

AU - Lindqvist, Johan

AU - Claeys, Kristl G

AU - Weis, Joachim

AU - Monforte, Mauro

AU - Tasca, Giorgio

AU - Moggio, Maurizio

AU - Figeac, Nicolas

AU - Zammit, Peter S

AU - Jungbluth, Heinz

AU - Fiorillo, Chiara

AU - Vissing, John

AU - Witting, Nanna

AU - Granzier, Henk

AU - Zanoteli, Edmar

AU - Hardeman, Edna C

AU - Wallgren-Pettersson, Carina

AU - Ochala, Julien

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

U2 - 10.1007/s00401-019-02034-8

DO - 10.1007/s00401-019-02034-8

M3 - Journal article

VL - 138

SP - 477

EP - 495

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 3

ER -

ID: 58155927