Roles of the lamin A-specific tail region in the localization to sites of nuclear envelope rupture.

Autor:	Kono Y; Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan.; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan.; Faculty of Frontier Engineering, Institute of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan., Pack CG; Convergence Medicine Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul 05505, Korea.; Department of Biomedical Engineering, University of Ulsan College of Medicine, Seoul 05505, Korea., Ichikawa T; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan., Komatsubara A; School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8503, Japan., Adam SA; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 USA., Miyazawa K; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan.; Faculty of Frontier Engineering, Institute of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan., Rolas L; Centre for Microvascular Research, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, United Kingdom., Nourshargh S; Centre for Microvascular Research, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, United Kingdom., Medalia O; Department of Biochemistry, University of Zurich, Zurich 8057, Switzerland., Goldman RD; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 USA., Fukuma T; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan.; Faculty of Frontier Engineering, Institute of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan., Kimura H; Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan.; School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8503, Japan., Shimi T; Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan.; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan.
Jazyk:	angličtina
Zdroj:	PNAS nexus [PNAS Nexus] 2024 Nov 21; Vol. 3 (12), pp. pgae527. Date of Electronic Publication: 2024 Nov 21 (Print Publication: 2024).
DOI:	10.1093/pnasnexus/pgae527
Abstrakt:	The nuclear lamina (NL) lines the nuclear envelope (NE) to maintain nuclear structure in metazoan cells. The major NL components, the nuclear lamins contribute to the protection against NE rupture induced by mechanical stress. Lamin A (LA) and a short form of the splicing variant lamin C (LC) are diffused from the nucleoplasm to sites of NE rupture in immortalized mouse embryonic fibroblasts (MEFs). LA localization to the rupture sites is significantly slow and weak compared with LC, but the underlying mechanism remains unknown. In this study, wild-type (WT), Hutchinson-Gilford Progeria syndrome (HGPS) knock-in MEFs expressing progerin (PG, an LA mutant lacking the second proteolytic cleavage site), and LA/C-knockout MEFs transiently and heterogeneously expressing LA/C WTs and mutants fused to mEmerald are examined before and after NE rupture induced by single-cell compression and laser microirradiation. The farnesylation at the CaaX motif of unprocessed LA and the inhibition of the second proteolytic cleavage decrease the nucleoplasmic pool and slow the localization to the rupture sites in a long-time window (60-70 min) after the induction of NE rupture. Our data could explain the defective repair of NE rupture in HGPS through the farnesylation at the CaaX motif of unprocessed progerin. In addition, unique segments in LA-specific tail region cooperate with each other to inhibit the rapid accumulation within a short-time window (3 min) that is also observed with LC. (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)
Databáze:	MEDLINE
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