Abstract |
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.
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Authors | Svetlana Piatnitskaia, Masahiko Takahashi, Hiroki Kitaura, Yoshinori Katsuragi, Taichi Kakihana, Lu Zhang, Akiyoshi Kakita, Yuriko Iwakura, Hiroyuki Nawa, Takeshi Miura, Takeshi Ikeuchi, Toshifumi Hara, Masahiro Fujii |
Journal | Scientific reports
(Sci Rep)
Vol. 9
Issue 1
Pg. 10591
(07 22 2019)
ISSN: 2045-2322 [Electronic] England |
PMID | 31332267
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- USP10 protein, human
- USP10 protein, mouse
- tau Proteins
- Ubiquitin Thiolesterase
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Topics |
- 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)
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