論文 - 詳細
| RRC ID | 81388 |
|---|---|
| 著者 | Takahashi M, Kitaura H, Kakita A, Kakihana T, Katsuragi Y, Onodera O, Iwakura Y, Nawa H, Komatsu M, Fujii M. |
| タイトル | USP10 Inhibits Aberrant Cytoplasmic Aggregation of TDP-43 by Promoting Stress Granule Clearance. |
| ジャーナル | Mol Cell Biol |
| Abstract |
TAR DNA-binding protein 43 (TDP-43) is a causative factor of amyotrophic lateral sclerosis (ALS). Cytoplasmic TDP-43 aggregates in neurons are a hallmark pathology of ALS. Under various stress conditions, TDP-43 localizes sequentially to two cytoplasmic protein aggregates, namely, stress granules (SGs) first and then aggresomes. Accumulating evidence suggests that delayed clearance of TDP-43-positive SGs is associated with pathological TDP-43 aggregates in ALS. We found that ubiquitin-specific protease 10 (USP10) promotes the clearance of TDP-43-positive SGs in cells treated with proteasome inhibitor, thereby promoting the formation of TDP-43-positive aggresomes, and the depletion of USP10 increases the amount of insoluble TDP-35, a cleaved product of TDP-43, in the cytoplasm. TDP-35 interacted with USP10 in an RNA-binding-dependent manner; however, impaired RNA binding of TDP-35 reduced the localization in SGs and aggresomes and induced USP10-negative TDP-35 aggregates. Immunohistochemistry showed that most of the cytoplasmic TDP-43/TDP-35 aggregates in the neurons of ALS patients were USP10 negative. Our findings suggest that USP10 inhibits aberrant aggregation of TDP-43/TDP-35 in the cytoplasm of neuronal cells by promoting the clearance of TDP-43/TDP-35-positive SGs and facilitating the formation of TDP-43/TDP-35-positive aggresomes. |
| 巻・号 | 42(3) |
| ページ | e0039321 |
| 公開日 | 2022-3-17 |
| DOI | 10.1128/MCB.00393-21 |
| PMID | 35007165 |
| PMC | PMC8929388 |
| MeSH | Amyotrophic Lateral Sclerosis* / genetics Cytoplasm / metabolism Cytoplasmic Granules / metabolism DNA-Binding Proteins / metabolism Humans RNA / metabolism Stress Granules Ubiquitin Thiolesterase / metabolism |
| IF | 3.611 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |