| Project/Area Number |
16K07700
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied biochemistry
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| Research Institution | Nagahama Institute of Bio-Science and Technology |
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Principal Investigator |
Kamemura Kazuo 長浜バイオ大学, バイオサイエンス学部, 准教授 (00399437)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | FETタンパク質 / FUS / EWS / TAF15 / 前頭側頭葉変性症 / 翻訳後修飾 / O-GlcNAc / グリコシル化 / タンパク質 / 発現制御 |
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| Outline of Final Research Achievements |
The FET protein family includes fused in sarcoma (FUS), Ewing sarcoma protein (EWS), and TATA binding protein-associated factor 15 (TAF15). Of the FET protein family, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. In this study, the glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. These results indicate that glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins and may help to prevent EWS from forming uncontrolled aggregates and accumulating in pathological inclusion bodies in the neurodegenerative diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
三大神経変性疾患の１つに前頭側頭葉変性症（FTLD）がある。FTLDは、病状を呈する神経細胞において異常凝集体を形成するタンパク質の種類に応じてサブタイプに分類されており、その１つにFTLD-FUSがある。FTLD-FUSでは、EWS以外のFETタンパク質（FUSとTAF15）が異常封入体を形成することが報告されているが、FETタンパク質間で凝集特性に差異を生じる原因は不明であった。よって、本研究の成果は、FTLD-FUSの病因解明に資する新たな知見である。
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