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Cited by 159Alzheimer's disease research and treatmentsRNA Research and SplicingAmyotrophic Lateral Sclerosis Research

TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau

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Ash, Peter E. A., Lei, Shuwen, Shattuck, Jenifer, Boudeau, Samantha, Carlomagno, Yari, Medalla, Maria, Mashimo, Bryce L., Socorro, Guillermo +9 more·2021·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2014188118PMC PMC7936275
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Abstract

Significance: Phase separation of proteins is increasingly thought to play a fundamental role in biological processes. Recent studies show that tau protein phase separates, but the biological significance is unknown since artificial crowding agents are typically used and the resulting tau is not toxic. We now demonstrate that TIA1 potentiates RNA-mediated phase separation of tau, thereby enabling a process that occurs at physiological concentrations and also directs the formation of biologically active, highly neurotoxic oligomeric tau. Coordinated phase separation of functionally related proteins provides a general mechanism through which membraneless organelles can direct biological activities.

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Authors
Ash, P. E. A., Lei, S., Shattuck, J., Boudeau, S., Carlomagno, Y., Medalla, M., Mashimo, B. L., Socorro, G., Al-Mohanna, L. F. A., Jiang, L., Öztürk, M. M., Knobel, M., Ivanov, P., Petrucelli, L., Wegmann, S., Kanaan, N. M., & Wolozin, B.
Affiliations
  • Boston University (US)
  • Mayo Clinic in Florida (US)
  • Brigham and Women's Hospital (US)
  • German Center for Neurodegenerative Diseases (DE)
  • Michigan State University (US)
Corresponding author
Wolozin, Benjamin
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2021-02-22
Volume
118
Issue
9
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2014188118
PMC
PMC7936275
OpenAlex
W3132154451
Cited by
159
References
11
Citations by year
2026: 31 · 2025: 29 · 2024: 31 · 2023: 28 · 2022: 29 · 2021: 11
FWCI
15.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DZNE Pub (submittedVersion)
Funders
  • HHS | National Institutes of Health (AG050471, NS089544, AG056318, AG064932, AG061706)
  • BrightFocus Foundation (CA2020002)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
tau protein, TIA-1, phase separation, stress granules, RNA-binding proteins, tau oligomers, neurodegeneration, biomolecular condensates, G3BP1, crowding agents, protein toxicity
MeSH terms
RNA Recognition Motif Proteins, T-Cell Intracellular Antigen-1, Amyloid, Humans, Neurons, Protein Binding, Recombinant Proteins, tau Proteins, Neurodegenerative Diseases, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Aggregation, Pathological, Protein Aggregates

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