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Pathogenic tau decreases nuclear tension in cultured neurons
Neurodegenerative tauopathies, including Alzheimer’s disease, are pathologically defined by the presence of aggregated forms of tau protein in brains of affected individuals. Previous studies report that the negative effects of pathogenic tau on the actin cytoskeleton and microtubules cause a toxic...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901542/ https://www.ncbi.nlm.nih.gov/pubmed/36756194 http://dx.doi.org/10.3389/fragi.2023.1058968 |
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author | Sohn, Claira Ma, Jiacheng Ray, William J. Frost, Bess |
author_facet | Sohn, Claira Ma, Jiacheng Ray, William J. Frost, Bess |
author_sort | Sohn, Claira |
collection | PubMed |
description | Neurodegenerative tauopathies, including Alzheimer’s disease, are pathologically defined by the presence of aggregated forms of tau protein in brains of affected individuals. Previous studies report that the negative effects of pathogenic tau on the actin cytoskeleton and microtubules cause a toxic destabilization of the lamin nucleoskeleton and formation of nuclear invaginations and blebs. Based on the known function of the nucleus as a mechanosensor, as well as the high incidence of nuclear pleomorphism in human Alzheimer’s disease and related tauopathies, we investigated the effects of pathogenic tau on nuclear tension. We first find that tau-dependent nuclear envelope invagination and relocalization of LInker of Nucleoskeleton and Cytoskeleton (LINC) complex components are conserved in a newly-developed neuroblastoma cell line that features doxycycline-inducible expression of a tau mutant associated with autosomal dominant frontotemporal dementia. We next determine that a Förster resonance energy transfer (FRET)-based sensor of nuclear tension responds to cytoskeletal stabilization and destabilization when expressed in neuroblastoma cells. Using this nuclear tension sensor, we find that induced expression of pathogenic tau is sufficient to decrease nuclear tension. This work provides the initial proof-of-concept evidence that pathogenic forms of tau alter nuclear tension, paving the way for the future study of altered nuclear mechanosensing in the context of tau-mediated neurodegenerative disorders. |
format | Online Article Text |
id | pubmed-9901542 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99015422023-02-07 Pathogenic tau decreases nuclear tension in cultured neurons Sohn, Claira Ma, Jiacheng Ray, William J. Frost, Bess Front Aging Aging Neurodegenerative tauopathies, including Alzheimer’s disease, are pathologically defined by the presence of aggregated forms of tau protein in brains of affected individuals. Previous studies report that the negative effects of pathogenic tau on the actin cytoskeleton and microtubules cause a toxic destabilization of the lamin nucleoskeleton and formation of nuclear invaginations and blebs. Based on the known function of the nucleus as a mechanosensor, as well as the high incidence of nuclear pleomorphism in human Alzheimer’s disease and related tauopathies, we investigated the effects of pathogenic tau on nuclear tension. We first find that tau-dependent nuclear envelope invagination and relocalization of LInker of Nucleoskeleton and Cytoskeleton (LINC) complex components are conserved in a newly-developed neuroblastoma cell line that features doxycycline-inducible expression of a tau mutant associated with autosomal dominant frontotemporal dementia. We next determine that a Förster resonance energy transfer (FRET)-based sensor of nuclear tension responds to cytoskeletal stabilization and destabilization when expressed in neuroblastoma cells. Using this nuclear tension sensor, we find that induced expression of pathogenic tau is sufficient to decrease nuclear tension. This work provides the initial proof-of-concept evidence that pathogenic forms of tau alter nuclear tension, paving the way for the future study of altered nuclear mechanosensing in the context of tau-mediated neurodegenerative disorders. Frontiers Media S.A. 2023-01-23 /pmc/articles/PMC9901542/ /pubmed/36756194 http://dx.doi.org/10.3389/fragi.2023.1058968 Text en Copyright © 2023 Sohn, Ma, Ray and Frost. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Aging Sohn, Claira Ma, Jiacheng Ray, William J. Frost, Bess Pathogenic tau decreases nuclear tension in cultured neurons |
title | Pathogenic tau decreases nuclear tension in cultured neurons |
title_full | Pathogenic tau decreases nuclear tension in cultured neurons |
title_fullStr | Pathogenic tau decreases nuclear tension in cultured neurons |
title_full_unstemmed | Pathogenic tau decreases nuclear tension in cultured neurons |
title_short | Pathogenic tau decreases nuclear tension in cultured neurons |
title_sort | pathogenic tau decreases nuclear tension in cultured neurons |
topic | Aging |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901542/ https://www.ncbi.nlm.nih.gov/pubmed/36756194 http://dx.doi.org/10.3389/fragi.2023.1058968 |
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