RNA binding proteins co-localize with small tau inclusions in tauopathy
Abstract 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) th...
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doaj-1ff29ffa3bc645ae9a23707f55eb60f22020-11-25T01:32:32ZengBMCActa Neuropathologica Communications2051-59602018-08-016111410.1186/s40478-018-0574-5RNA binding proteins co-localize with small tau inclusions in tauopathyBrandon F. Maziuk0Daniel J. Apicco1Anna Lourdes Cruz2Lulu Jiang3Peter E. A. Ash4Edroaldo Lummertz da Rocha5Cheng Zhang6Wai Haung Yu7John Leszyk8Jose F. Abisambra9Hu Li10Benjamin Wolozin11Department of Pharmacology and Experimental TherapeuticsDepartment of Pharmacology and Experimental TherapeuticsDepartment of Pharmacology and Experimental TherapeuticsDepartment of Pharmacology and Experimental TherapeuticsDepartment of Pharmacology and Experimental TherapeuticsMayo ClinicMayo ClinicDepartment of Pathology and Cell Biology, Taub Institute for Alzheimer’s Disease Research, Columbia University Medical CenterUniversity of Massachusetts Medical CenterSanders-Brown Center on Aging, Department of Physiology, Spinal Cord and Brain Injury Research Center, and Epilepsy Center, University of KentuckyMayo ClinicDepartment of Pharmacology and Experimental TherapeuticsAbstract 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.http://link.springer.com/article/10.1186/s40478-018-0574-5Alzheimer’s diseaseNeurofibrillary tangleImmunohistochemistryMass spectrometryProtein interactomeProtein aggregation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Brandon F. Maziuk Daniel J. Apicco Anna Lourdes Cruz Lulu Jiang Peter E. A. Ash Edroaldo Lummertz da Rocha Cheng Zhang Wai Haung Yu John Leszyk Jose F. Abisambra Hu Li Benjamin Wolozin |
spellingShingle |
Brandon F. Maziuk Daniel J. Apicco Anna Lourdes Cruz Lulu Jiang Peter E. A. Ash Edroaldo Lummertz da Rocha Cheng Zhang Wai Haung Yu John Leszyk Jose F. Abisambra Hu Li Benjamin Wolozin RNA binding proteins co-localize with small tau inclusions in tauopathy Acta Neuropathologica Communications Alzheimer’s disease Neurofibrillary tangle Immunohistochemistry Mass spectrometry Protein interactome Protein aggregation |
author_facet |
Brandon F. Maziuk Daniel J. Apicco Anna Lourdes Cruz Lulu Jiang Peter E. A. Ash Edroaldo Lummertz da Rocha Cheng Zhang Wai Haung Yu John Leszyk Jose F. Abisambra Hu Li Benjamin Wolozin |
author_sort |
Brandon F. Maziuk |
title |
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_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_sort |
rna binding proteins co-localize with small tau inclusions in tauopathy |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2018-08-01 |
description |
Abstract 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. |
topic |
Alzheimer’s disease Neurofibrillary tangle Immunohistochemistry Mass spectrometry Protein interactome Protein aggregation |
url |
http://link.springer.com/article/10.1186/s40478-018-0574-5 |
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