USP10 is a critical factor for Tau-positive stress granule formation in neuronal cells

Sci Rep. 2019 Jul 22;9(1):10591. doi: 10.1038/s41598-019-47033-7.


Tau aggregates in neurons of brain lesions is a hallmark pathology of tauopathies, including Alzheimer's disease (AD). Recent studies suggest that the RNA-binding protein TIA1 initiates Tau aggregation by inducing the formation of stress granules (SGs) containing Tau. SGs are stress-inducible cytoplasmic protein aggregates containing many RNA-binding proteins that has been implicated as an initial site of multiple pathogenic protein aggregates in several neurodegenerative diseases. In this study, we found that ubiquitin-specific protease 10 (USP10) is a critical factor for the formation of Tau/TIA1/USP10-positive SGs. Proteasome inhibition or TIA1-overexpression in HT22 neuronal cells induced the formation of TIA1/Tau-positive SGs, and the formations were severely attenuated by depletion of USP10. In addition, the overexpression of USP10 without stress stimuli in HT22 cells induced TIA1/Tau/USP10-positive SGs in a deubiquitinase-independent manner. In AD brain lesions, USP10 was colocalized with Tau aggregates in the cell body of neurons. The present findings suggest that USP10 plays a key role in the initiation of pathogenic Tau aggregation in AD through SG formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Cytoplasmic Granules / metabolism*
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Ubiquitin Thiolesterase / metabolism*
  • tau Proteins / metabolism*


  • USP10 protein, human
  • USP10 protein, mouse
  • tau Proteins
  • Ubiquitin Thiolesterase