核酸を分解する膜透過型オートファジーのメカニズムと疾患との関連
| Project/Area Number |
18F18384
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
株田 智弘 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 室長 (70535765)
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| Co-Investigator(Kenkyū-buntansha) |
CONTU VIORICA 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 外国人特別研究員
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| Project Period (FY) |
2018-11-09 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2020: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2019: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2018: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | autophagy / Autophagy / neurodegeneration / RNautophagy / lysosome / SIDT2 / lysosomal degradation |
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| Outline of Annual Research Achievements |
Because already known lysosomal degradation pathways cannot fully account for total levels of lysosomal proteolysis in cells (Tong et al. 2020) and protein accumulation in cells is a hallmark of neurodegenerative diseases, we sought for novel protein degradation pathways in lysosomes.
We found that cytosolic proteins are imported into lysosomes by a direct uptake mechanism which is distinct from any known pathways, and then degraded. SIDT2 mediates the translocation and contributes conspicuously to the lysosomal degradation of a wide range of cytosolic proteins in cells at the constitutive level (nutrient-rich condition). We also identified a dominant-negative mutation in SIDT2 which causes familial neuropathy and distal myopathy with rimmed vacuoles in humans and confirmed that Sidt2 knockout mice recapitulate the typical features of the disease.
These results reveal previously unknown pathway of proteolysis in lysosomes and highlight the importance of lysosomal degradation of proteins in human physiology and pathophysiology.
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| Research Progress Status |
令和2年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和2年度が最終年度であるため、記入しない。
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Report
(3 results)
Research Products
(5 results)
