Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1

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 h...

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Autores principales:	Christine Schwartz, Martina Fischer, Kamel Mamchaoui, Anne Bigot, Thevy Lok, Claude Verdier, Alain Duperray, Richard Michel, Ian Holt, Thomas Voit, Suzanna Quijano-Roy, Gisèle Bonne, Catherine Coirault
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d11533a11abc4004a70805683a076dcf
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spelling	oai:doaj.org-article:d11533a11abc4004a70805683a076dcf2021-12-02T15:04:54ZLamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD110.1038/s41598-017-01324-z2045-2322https://doaj.org/article/d11533a11abc4004a70805683a076dcf2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01324-zhttps://doaj.org/toc/2045-2322Abstract 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.Christine SchwartzMartina FischerKamel MamchaouiAnne BigotThevy LokClaude VerdierAlain DuperrayRichard MichelIan HoltThomas VoitSuzanna Quijano-RoyGisèle BonneCatherine CoiraultNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christine Schwartz Martina Fischer Kamel Mamchaoui Anne Bigot Thevy Lok Claude Verdier Alain Duperray Richard Michel Ian Holt Thomas Voit Suzanna Quijano-Roy Gisèle Bonne Catherine Coirault Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1
description	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.
format	article
author	Christine Schwartz Martina Fischer Kamel Mamchaoui Anne Bigot Thevy Lok Claude Verdier Alain Duperray Richard Michel Ian Holt Thomas Voit Suzanna Quijano-Roy Gisèle Bonne Catherine Coirault
author_facet	Christine Schwartz Martina Fischer Kamel Mamchaoui Anne Bigot Thevy Lok Claude Verdier Alain Duperray Richard Michel Ian Holt Thomas Voit Suzanna Quijano-Roy Gisèle Bonne Catherine Coirault
author_sort	Christine Schwartz
title	Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1
title_short	Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1
title_full	Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1
title_fullStr	Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1
title_full_unstemmed	Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1
title_sort	lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through fhod1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d11533a11abc4004a70805683a076dcf
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Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1

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