The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair

20 Pág.

Detalhes bibliográficos
Autores: Wallis, Samuel S., Ventimiglia, Leandro, Otigbah, Evita, Infante, Elvira, Cuesta-Geijo, Miguel Ángel, Kidiyoor, Gururaj Rao, Carbajal, Maria Alejandra, Fleck, Roland, Foiani, Marco, Garcia-Manyes, Sergi, Martin-Serrano, Juan, Agromayor, Monica
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/372469
Acesso em linha:http://hdl.handle.net/10261/372469
https://api.elsevier.com/content/abstract/scopus_id/85120169353
Access Level:acceso abierto
Palavra-chave:ESCRT
LINC complex
Mechanosensing
Membrane repair
Nuclear envelope
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spelling The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repairWallis, Samuel S.Ventimiglia, LeandroOtigbah, EvitaInfante, ElviraCuesta-Geijo, Miguel ÁngelKidiyoor, Gururaj RaoCarbajal, Maria AlejandraFleck, RolandFoiani, MarcoGarcia-Manyes, SergiMartin-Serrano, JuanAgromayor, MonicaESCRTLINC complexMechanosensingMembrane repairNuclear envelope20 Pág.Transient nuclear envelope ruptures during interphase (NERDI) occur due to cytoskeletal compressive forces at sites of weakened lamina, and delayed NERDI repair results in genomic instability. Nuclear envelope (NE) sealing is completed by endosomal sorting complex required for transport (ESCRT) machinery. A key unanswered question is how local compressive forces are counteracted to allow efficient membrane resealing. Here, we identify the ESCRT-associated protein BROX as a crucial factor required to accelerate repair of the NE. Critically, BROX binds Nesprin-2G, a component of the linker of nucleoskeleton and cytoskeleton complex (LINC). This interaction promotes Nesprin-2G ubiquitination and facilitates the relaxation of mechanical stress imposed by compressive actin fibers at the rupture site. Thus, BROX rebalances excessive cytoskeletal forces in cells experiencing NE instability to promote effective NERDI repair. Our results demonstrate that BROX coordinates mechanoregulation with membrane remodeling to ensure the maintenance of nuclear-cytoplasmic compartmentalization and genomic stability.This work was supported by awards from the BBSRC (BB/N000501/1) and the King’s Health Partners R&D research fund (R151001) to M.A.; the Wellcome Trust (WT102871MA) to J.M.-S.; the European Commission (FET Proactive 731957), EPSRC (EP/M022536/1), Leverhulme Trust (RPG-2015-225 and RL-2016-015), Wellcome Trust (212218/Z/18/Z) and Royal Society (RSWF/R3/183006) to S.G.-M.; and the Italian Association for Cancer Research (AIRC) to M.F. S.S.W. was supported by the King’s Bioscience Institute and the Guy’s and St Thomas’ Charity Prize Ph.D. Programme in Biomedical and Translational Science. E.O. is supported by the UK Medical Research Council (MR/N013700/1) and is a King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences.Peer reviewedElsevierEuropean CommissionWallis, Samuel S. [0000-0001-6103-1933]Ventimiglia, Leandro [0000-0002-2872-1497]Infante, Elvira [0000-0002-9883-8391]Cuesta-Geijo, Miguel Ángel [0000-0003-4694-1968]Kidiyoor, Gururaj Rao [0000-0002-8887-7696]Carbajal, Maria Alejandra [0000-0002-3120-0166]Fleck, Roland [0000-0003-1542-6218]Foiani, Marco [0000-0003-4795-834X]Garcia-Manyes, Sergi [0000-0001-5140-2606]Martin-Serrano, Juan [0000-0002-8183-3914]Agromayor, Monica [0000-0001-6477-1750]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/372469https://api.elsevier.com/content/abstract/scopus_id/85120169353reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/731957/Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)publisherhttps://doi.org/10.1016/j.devcel.2021.10.022Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3724692026-05-22T06:33:51Z
dc.title.none.fl_str_mv The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
title The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
spellingShingle The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
Wallis, Samuel S.
ESCRT
LINC complex
Mechanosensing
Membrane repair
Nuclear envelope
title_short The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
title_full The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
title_fullStr The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
title_full_unstemmed The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
title_sort The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair
dc.creator.none.fl_str_mv Wallis, Samuel S.
Ventimiglia, Leandro
Otigbah, Evita
Infante, Elvira
Cuesta-Geijo, Miguel Ángel
Kidiyoor, Gururaj Rao
Carbajal, Maria Alejandra
Fleck, Roland
Foiani, Marco
Garcia-Manyes, Sergi
Martin-Serrano, Juan
Agromayor, Monica
author Wallis, Samuel S.
author_facet Wallis, Samuel S.
Ventimiglia, Leandro
Otigbah, Evita
Infante, Elvira
Cuesta-Geijo, Miguel Ángel
Kidiyoor, Gururaj Rao
Carbajal, Maria Alejandra
Fleck, Roland
Foiani, Marco
Garcia-Manyes, Sergi
Martin-Serrano, Juan
Agromayor, Monica
author_role author
author2 Ventimiglia, Leandro
Otigbah, Evita
Infante, Elvira
Cuesta-Geijo, Miguel Ángel
Kidiyoor, Gururaj Rao
Carbajal, Maria Alejandra
Fleck, Roland
Foiani, Marco
Garcia-Manyes, Sergi
Martin-Serrano, Juan
Agromayor, Monica
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Wallis, Samuel S. [0000-0001-6103-1933]
Ventimiglia, Leandro [0000-0002-2872-1497]
Infante, Elvira [0000-0002-9883-8391]
Cuesta-Geijo, Miguel Ángel [0000-0003-4694-1968]
Kidiyoor, Gururaj Rao [0000-0002-8887-7696]
Carbajal, Maria Alejandra [0000-0002-3120-0166]
Fleck, Roland [0000-0003-1542-6218]
Foiani, Marco [0000-0003-4795-834X]
Garcia-Manyes, Sergi [0000-0001-5140-2606]
Martin-Serrano, Juan [0000-0002-8183-3914]
Agromayor, Monica [0000-0001-6477-1750]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv ESCRT
LINC complex
Mechanosensing
Membrane repair
Nuclear envelope
topic ESCRT
LINC complex
Mechanosensing
Membrane repair
Nuclear envelope
description 20 Pág.
publishDate 2021
dc.date.none.fl_str_mv 2021
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/372469
https://api.elsevier.com/content/abstract/scopus_id/85120169353
url http://hdl.handle.net/10261/372469
https://api.elsevier.com/content/abstract/scopus_id/85120169353
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/731957/
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)
publisher
https://doi.org/10.1016/j.devcel.2021.10.022
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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