Schwartz, C;
Fischer, M;
Mamchaoui, K;
Bigot, A;
Lok, T;
Verdier, C;
Duperray, A;
... Coirault, C; + view all
(2017)
Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1.
Scientific Reports
, 7
, Article 1253. 10.1038/s41598-017-01324-z.
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Abstract
LINC complexes are crucial for the response of muscle cell precursors to the rigidity of their environment, but the mechanisms explaining this behaviour are not known. Here we show that pathogenic mutations in LMNA or SYNE-1 responsible for severe muscle dystrophies reduced the ability of human muscle cell precursors to adapt to substrates of different stiffness. Plated on muscle-like stiffness matrix, mutant cells exhibited contractile stress fibre accumulation, increased focal adhesions, and higher traction force than controls. Inhibition of Rho-associated kinase (ROCK) prevented cytoskeletal defects, while inhibiting myosin light chain kinase or phosphorylation of focal adhesion kinase was ineffective. Depletion or inactivation of a ROCK-dependent regulator of actin remodelling, the formin FHOD1, largely rescued morphology in mutant cells. The functional integrity of lamin and nesprin-1 is thus required to modulate the FHOD1 activity and the inside-out mechanical coupling that tunes the cell internal stiffness to match that of its soft, physiological-like environment.
| Type: | Article |
|---|---|
| Title: | Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-017-01324-z |
| Publisher version: | https://doi.org/10.1038/s41598-017-01324-z |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Cell adhesion, Physiology |
| 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 Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10092198 |
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