Related Experiment Video

Updated: Jul 15, 2026

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
12:57

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

Published on: January 8, 2015

TAF15 amyloids propagate via defined motifs in a prion-like fashion

Katerina Konstantoulea1,2,3, Laxmikant Gadhe1,2,3, Frank Goodavish1,2,3

  • 1Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Nature Communications
|July 13, 2026
PubMed

Insights

TATA-box binding protein-associated factor 15 (TAF15) forms amyloid fibrils and propagates like a prion in cells. Specific protein motifs drive TAF15 self-assembly, offering insights into frontotemporal lobar degeneration (FTLD) mechanisms.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • TATA-box binding protein-associated factor 15 (TAF15) is implicated in frontotemporal lobar degeneration (FTLD).
  • The molecular basis of TAF15 aggregation in FTLD pathogenesis is not well understood.
  • TAF15 is an RNA-binding protein and a key component of pathological fibrils in some FTLD cases.

Purpose of the Study:

  • To investigate the aggregation properties of TAF15.
  • To develop a biosensor for monitoring TAF15 propagation.
  • To identify sequence determinants governing TAF15 self-assembly and propagation.

Main Methods:

  • Formation of amyloid fibrils from recombinant TAF15.
  • Development of a cellular biosensor to detect TAF15 seeding.
  • Analysis of pathological aggregates from FTLD patient brains.
  • Computational and peptide-based mapping of TAF15 aggregation motifs.

Main Results:

  • TAF15 forms amyloid fibrils under physiological conditions.
  • TAF15 fibrils and patient-derived aggregates exhibit prion-like seeding behavior in biosensor cells.
  • A cross-seeding barrier exists between TAF15 and the related protein FUS.
  • Aggregation-prone motifs in the low-complexity domain stabilize fibril cores and drive TAF15 propagation.

Conclusions:

  • TAF15 is an amyloid-forming protein with prion-like propagation characteristics.
  • Specific sequence motifs within TAF15's low-complexity domain are critical for its aggregation and propagation.
  • These findings provide a mechanistic understanding of FTLD-TAF15 and suggest potential therapeutic targets.

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