| Project/Area Number |
26460557
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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 |
Virology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
UCHIYAMA Keiji 徳島大学, 先端酵素学研究所(次世代), 准教授 (60294039)
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| Co-Investigator(Renkei-kenkyūsha) |
SAKAGUCHI Suehiro 徳島大学, 先端酵素学研究所, 教授 (60274635)
YANO Masashi 徳島大学, 先端酵素学研究所, 技術専門職員 (10531858)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | プリオン / プリオン病 / 異常プリオン / Sortilin / ソーティング / レトロマー / VPS35 / ソーティリン / プリオン感染 / レトロマー複合体 / タンパク質分解 / プリオン分解 / タパク質分解 / プリオン高感受性 / ンソーティリン欠損マウス / ソーティリン欠損細胞 |
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| Outline of Final Research Achievements |
We have identified a novel prion (PrP)-binding protein, Sortilin, and found that it mediates trafficking of PrP to late endosomal/lysosomal compartments. Sortilin dysfunction causes delayed degradation and accelerated accumulation of abnornal prion protein (PrPSc). Remarkably, prion infection reduces Sortilin expression by inhibiting retromer-mediated retrieval of Sortilin from endosomes to the TGN, resulting in its overdegradation in lysosomes. These results indicate that PrPSc is protected from lysosomal degradation and accumulated by reducing Sortilin expression by itself. Moreover, recovery of Sortilin function by oversxpression of Sortilin significantly reduced PrPSc in prion infected cells. We also showed that Sortilin deficiency in mice accelerates PrPSc accumulation and reduces incubation and survival period for prions.
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