Evidence mapPaperPMID 36626563Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Cytosolic condensates rich in polyserine define subcellular sites of tau aggregation.

Evan Lester, Meaghan Van Alstyne, Kathleen L McCann, Spoorthy Reddy, Li Yi Cheng, Jeff Kuo, James Pratt, Roy Parker

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Polyserine domains are toxic and exacerbate tau pathology in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Polyserine-tau interactions modulate tau fibrillization.The Journal of biological chemistry · 2025
    Article
  7. Loss of age-associated increase in mbioRxiv : the preprint server for biology · 2025
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. The influence of APOEActa neuropathologica · 2024
    Article
  17. Article
  18. Post-Translational Modifications Control Phase Transitions of Tau.bioRxiv : the preprint server for biology · 2024
    Article
  19. Article
  20. Nuclear face of Tau: an inside player in neurodegeneration.Acta neuropathologica communications · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Evan LesterMedical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
Meaghan Van AlstyneDepartment of Biochemistry, University of Colorado, Boulder, CO 80303.
Kathleen L McCannDepartment of Biochemistry, University of Colorado, Boulder, CO 80303.
Spoorthy ReddyDepartment of Biochemistry, University of Colorado, Boulder, CO 80303.
Li Yi ChengDepartment of Biochemistry, University of Colorado, Boulder, CO 80303.
Jeff KuoDepartment of Biochemistry, University of Colorado, Boulder, CO 80303.
James PrattDepartment of Biochemistry, University of Colorado, Boulder, CO 80303.
Roy ParkerDepartment of Biochemistry, University of Colorado, Boulder, CO 80303.ORCID 0000-0002-8412-4152
University of Colorado Boulder · US

Funding

REGULATION OF MRNA TURNOVER IN YEASTR01GM045443 · UNIVERSITY OF ARIZONA · 1991 to 2003
$818k
mRNA Decapping in YeastR37GM045443 · UNIVERSITY OF ARIZONA · 2004 to 2005
$676k
NIA NIH HHS F30 AG063468NIGMS NIH HHS R01 GM045443NIGMS NIH HHS R37 GM045443
6 · The paper itself

Abstract

Tau aggregates are a hallmark of multiple neurodegenerative diseases and can contain RNAs and RNA-binding proteins, including serine/arginine repetitive matrix protein 2 (SRRM2) and pinin (PNN). However, how these nuclear proteins mislocalize and their influence on the prion-like propagation of tau aggregates is unknown. We demonstrate that polyserine repeats in SRRM2 and PNN are necessary and sufficient for recruitment to tau aggregates. Moreover, we show tau aggregates preferentially grow in association with endogenous cytoplasmic assemblies-mitotic interchromatin granules and cytoplasmic speckles (CSs)-which contain SRRM2 and PNN. Polyserine overexpression in cells nucleates assemblies that are sites of tau aggregate growth. Further, modulating the levels of polyserine-containing proteins results in a corresponding change in tau aggregation. These findings define a specific protein motif, and cellular condensates, that promote tau aggregate propagation. As CSs form in induced pluripotent stem cell (iPSC) derived neurons under inflammatory or hyperosmolar stress, they may affect tau aggregate propagation in neurodegenerative disease.

Indexed as

Alzheimer DiseaseNeurodegenerative DiseasesTauopathiesHumansPeptidestau ProteinsPeptidespolyserinetau ProteinsAlzheimer’s diseasefrontotemporal dementiaRNA-binding proteinsSRRM2tau

Identifiers

PMID36626563
PMCPMC9934293
OpenAlexW4315437042

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.