Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783343551065620480 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6069705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT maziukbrandonf rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT apiccodanielj rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT cruzannalourdes rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT jianglulu rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT ashpeterea rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT darochaedroaldolummertz rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT zhangcheng rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT yuwaihaung rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT leszykjohn rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT abisambrajosef rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT lihu rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy AT wolozinbenjamin rnabindingproteinscolocalizewithsmalltauinclusionsintauopathy |