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A lamin A/C variant causing striated muscle disease provides insights into filament organization

Title: A lamin A/C variant causing striated muscle disease provides insights into filament organization
Authors: Kronenberg-Tenga, Rafael; Tatli, Meltem; Eibauer, Matthias; Wu, Wei; Shin, Ji-Yeon; Bonne, Gisèle; Worman, Howard J; Medalia, Ohad
Source: Kronenberg-Tenga, Rafael; Tatli, Meltem; Eibauer, Matthias; Wu, Wei; Shin, Ji-Yeon; Bonne, Gisèle; Worman, Howard J; Medalia, Ohad (2021). A lamin A/C variant causing striated muscle disease provides insights into filament organization. Journal of Cell Science, 134(6):jcs256156.
Publisher Information: The Company of Biologists
Publication Year: 2021
Collection: University of Zurich (UZH): ZORA (Zurich Open Repository and Archive
Subject Terms: Department of Biochemistry; 570 Life sciences; biology; 610 Medicine & health
Description: The LMNA gene encodes the A-type lamins, which polymerize into ∼3.5-nm-thick filaments and, together with B-type lamins and associated proteins, form the nuclear lamina. Mutations in LMNA cause a wide variety of pathologies. In this study, we analyzed the nuclear lamina of embryonic fibroblasts from LmnaH222P/H222P mice, which develop cardiomyopathy and muscular dystrophy. Although the organization of the lamina appeared unaltered, there were changes in chromatin and B-type lamin expression. An increase in nuclear size and consequently a relative reduction in heterochromatin near the lamina allowed for a higher resolution structural analysis of lamin filaments using cryo-electron tomography. This was most apparent when visualizing lamin filaments in situ and using a nuclear extraction protocol. Averaging of individual segments of filaments in LmnaH222P/H222P mouse fibroblasts resolved two polymers that constitute the mature filaments. Our findings provide better views of the organization of lamin filaments and the effect of a striated muscle disease-causing mutation on nuclear structure.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 0021-9533
Relation: https://www.zora.uzh.ch/id/eprint/209838/1/Kornenberg-Tenga_et_al_2021.pdf; info:pmid/33536248; urn:issn:0021-9533
DOI: 10.1242/jcs.256156
Availability: https://www.zora.uzh.ch/id/eprint/209838/; https://doi.org/10.1242/jcs.256156
Rights: info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.2AA00379
Database: BASE