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

Autor:	Wallis SS; Department of Infectious Diseases, King's College London, Faculty of Life Sciences & Medicine, London SE1 9RT, UK., Ventimiglia LN; Department of Infectious Diseases, King's College London, Faculty of Life Sciences & Medicine, London SE1 9RT, UK., Otigbah E; Department of Infectious Diseases, King's College London, Faculty of Life Sciences & Medicine, London SE1 9RT, UK., Infante E; Department of Physics, Randall Centre for Cell and Molecular Biophysics, and London Centre for Nanotechnology, King's College London, London WC2R 2LS, UK., Cuesta-Geijo MA; Department of Infectious Diseases, King's College London, Faculty of Life Sciences & Medicine, London SE1 9RT, UK; Centro Nacional Instituto de Investigación y Tecnología Agraria y Alimentaria (CSIC), Ctra. de la Coruña Km 7.5, 28040 Madrid, Spain., Kidiyoor GR; Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Via Adamello 16, 20139 Milan, Italy; Università degli Studi di Milano, 20122 Milan, Italy., Carbajal MA; Centre for Ultrastructural Imaging, King's College London, London SE1 1UL, UK., Fleck RA; Centre for Ultrastructural Imaging, King's College London, London SE1 1UL, UK., Foiani M; Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Via Adamello 16, 20139 Milan, Italy; Università degli Studi di Milano, 20122 Milan, Italy., Garcia-Manyes S; Department of Physics, Randall Centre for Cell and Molecular Biophysics, and London Centre for Nanotechnology, King's College London, London WC2R 2LS, UK; the Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Martin-Serrano J; Department of Infectious Diseases, King's College London, Faculty of Life Sciences & Medicine, London SE1 9RT, UK. Electronic address: juan.martin_serrano@kcl.ac.uk., Agromayor M; Department of Infectious Diseases, King's College London, Faculty of Life Sciences & Medicine, London SE1 9RT, UK. Electronic address: monica.agromayor@kcl.ac.uk.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2021 Dec 06; Vol. 56 (23), pp. 3192-3202.e8. Date of Electronic Publication: 2021 Nov 23.
DOI:	10.1016/j.devcel.2021.10.022
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu