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RNA binding proteins co-localize with small tau inclusions in tauopathy

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are kn...

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Autores principales: Maziuk, Brandon F., Apicco, Daniel J., Cruz, Anna Lourdes, Jiang, Lulu, Ash, Peter E. A., da Rocha, Edroaldo Lummertz, Zhang, Cheng, Yu, Wai Haung, Leszyk, John, Abisambra, Jose F., Li, Hu, Wolozin, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069705/
https://www.ncbi.nlm.nih.gov/pubmed/30068389
http://dx.doi.org/10.1186/s40478-018-0574-5
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author Maziuk, Brandon F.
Apicco, Daniel J.
Cruz, Anna Lourdes
Jiang, Lulu
Ash, Peter E. A.
da Rocha, Edroaldo Lummertz
Zhang, Cheng
Yu, Wai Haung
Leszyk, John
Abisambra, Jose F.
Li, Hu
Wolozin, Benjamin
author_facet Maziuk, Brandon F.
Apicco, Daniel J.
Cruz, Anna Lourdes
Jiang, Lulu
Ash, Peter E. A.
da Rocha, Edroaldo Lummertz
Zhang, Cheng
Yu, Wai Haung
Leszyk, John
Abisambra, Jose F.
Li, Hu
Wolozin, Benjamin
author_sort Maziuk, Brandon F.
collection PubMed
description The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated that many of these proteins including hnRNPA0, EWSR1, PABP and RPL7 form insoluble aggregates as tau pathology develops. Immunohistochemical analysis of mouse and human brain tissues suggest a model of evolving pathological interaction, in which RBPs co-localize with pathological phospho-tau but occur adjacent to larger pathological tau inclusions. We suggest a model in which tau initially interacts with RBPs in small complexes, but evolves into isolated aggregated inclusions as tau pathology matures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0574-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-60697052018-08-03 RNA binding proteins co-localize with small tau inclusions in tauopathy Maziuk, Brandon F. Apicco, Daniel J. Cruz, Anna Lourdes Jiang, Lulu Ash, Peter E. A. da Rocha, Edroaldo Lummertz Zhang, Cheng Yu, Wai Haung Leszyk, John Abisambra, Jose F. Li, Hu Wolozin, Benjamin Acta Neuropathol Commun Research The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated that many of these proteins including hnRNPA0, EWSR1, PABP and RPL7 form insoluble aggregates as tau pathology develops. Immunohistochemical analysis of mouse and human brain tissues suggest a model of evolving pathological interaction, in which RBPs co-localize with pathological phospho-tau but occur adjacent to larger pathological tau inclusions. We suggest a model in which tau initially interacts with RBPs in small complexes, but evolves into isolated aggregated inclusions as tau pathology matures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0574-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-01 /pmc/articles/PMC6069705/ /pubmed/30068389 http://dx.doi.org/10.1186/s40478-018-0574-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Maziuk, Brandon F.
Apicco, Daniel J.
Cruz, Anna Lourdes
Jiang, Lulu
Ash, Peter E. A.
da Rocha, Edroaldo Lummertz
Zhang, Cheng
Yu, Wai Haung
Leszyk, John
Abisambra, Jose F.
Li, Hu
Wolozin, Benjamin
RNA binding proteins co-localize with small tau inclusions in tauopathy
title RNA binding proteins co-localize with small tau inclusions in tauopathy
title_full RNA binding proteins co-localize with small tau inclusions in tauopathy
title_fullStr RNA binding proteins co-localize with small tau inclusions in tauopathy
title_full_unstemmed RNA binding proteins co-localize with small tau inclusions in tauopathy
title_short RNA binding proteins co-localize with small tau inclusions in tauopathy
title_sort rna binding proteins co-localize with small tau inclusions in tauopathy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069705/
https://www.ncbi.nlm.nih.gov/pubmed/30068389
http://dx.doi.org/10.1186/s40478-018-0574-5
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