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Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy
http://hdl.handle.net/10069/38309
http://hdl.handle.net/10069/383099793ed5f-0131-42bb-a275-982647c84650
名前 / ファイル | ライセンス | アクション |
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IJMS19_1497.pdf (1.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-06-18 | |||||
タイトル | ||||||
タイトル | Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Cellular model | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Sarkosyl insoluble tau | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Super-resolution microscopy | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Tauopathy | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Matsumoto, Gen
× Matsumoto, Gen× Matsumoto, Kazuki× Kimura, Taeko× Suhara, Tetsuya× Higuchi, Makoto× Sahara, Naruhiko× Mori, Nozomu |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Neurofibrillary tangles composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases collectively termed tauopathy. To understand the mechanisms underlying the cause of tauopathy, precise cellular and animal models are required. Recent data suggest that the transient introduction of exogenous tau can accelerate the development of tauopathy in the brains of non-transgenic and transgenic mice expressing wild-type human tau. However, the transmission mechanism leading to tauopathy is not fully understood. In this study, we developed cultured-cell models of tauopathy representing a human tauopathy. Neuro2a (N2a) cells containing propagative tau filaments were generated by introducing purified tau fibrils. These cell lines expressed full-length (2N4R) human tau and the green fluorescent protein (GFP)-fused repeat domain of tau with P301L mutation. Immunocytochemistry and super-resolution microscopic imaging revealed that tau inclusions exhibited filamentous morphology and were composed of both full-length and repeat domain fragment tau. Live-cell imaging analysis revealed that filamentous tau inclusions are transmitted to daughter cells, resulting in yeast-prion-like propagation. By a standard method of tau preparation, both full-length tau and repeat domain fragments were recovered in sarkosyl insoluble fraction. Hyperphosphorylation of full-length tau was confirmed by the immunoreactivity of phospho-Tau antibodies and mobility shifts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These properties were similar to the biochemical features of P301L mutated human tau in a mouse model of tauopathy. In addition, filamentous tau aggregates in cells barely co-localized with ubiquitins, suggesting that most tau aggregates were excluded from protein degradation systems, and thus propagated to daughter cells. The present cellular model of tauopathy will provide an advantage for dissecting the mechanisms of tau aggregation and degradation and be a powerful tool for drug screening to prevent tauopathy. | |||||
書誌情報 |
International Journal of Molecular Sciences 巻 19, 号 5, p. 1497, 発行日 2018-05-17 |
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出版者 | ||||||
出版者 | MDPI AG | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 16616596 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 14220067 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/ijms19051497 | |||||
権利 | ||||||
権利情報 | c 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | International Journal of Molecular Sciences, 19(5), 1497; 2018 |