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

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

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Number of pages1
JournalActa Neuropathologica Communications
Volume6
Issue number1
DOIs
StatePublished - Aug 1 2018

Keywords

  • Alzheimer’s disease
  • Immunohistochemistry
  • Mass spectrometry
  • Neurofibrillary tangle
  • Protein aggregation
  • Protein interactome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Maziuk, B. F., Apicco, D. J., Cruz, A. L., Jiang, L., Ash, P. E. A., da Rocha, E. L., Zhang, C., Yu, W. H., Leszyk, J., Abisambra, J. F., Li, H., & Wolozin, B. (2018). RNA binding proteins co-localize with small tau inclusions in tauopathy. Acta Neuropathologica Communications, 6(1). https://doi.org/10.1186/s40478-018-0574-5