| Project/Area Number |
17K18135
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
General physiology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Yoshina Sawako 東京女子医科大学, 医学部, 講師 (00424672)
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| Project Period (FY) |
2017-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | C.elegans / ADAMTS9 / カルシウム調節 / ミトコンドリア保護 / フェブキソスタット / 寿命 / IP3R / IP3 / 小胞体 / 蛋白質輸送 / 分化 / 糖尿病 |
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| Outline of Final Research Achievements |
Our research revealed that when ADAMTS9/GON-1 is deactivated, it triggers an unusual release of calcium ions from the endoplasmic reticulum (ER) through the IP3 receptor, leading to a rise in cytosolic calcium levels. Subsequently, we identified that directly interact with the GON domain. Furthermore, we searched for genes that suppress the above-mentioned phenotype and found ERAD-related factors. This suggests that the GON domain plays a crucial role in regulating the degradation of IP3 receptors.
There is a link between aging and mitochondrial function. We showed that FBX protects mitochondria and prevents age-related muscle deterioration in C. elegans. We used C. elegans as a model for Duchenne muscular dystrophy (DMD), Parkinson’s disease, and tauopathy. We demonstrated that FBX is a candidate drug for treating all these models.
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| Academic Significance and Societal Importance of the Research Achievements |
小胞体（ER）は蛋白質を合成・輸送し、多様な生命活動の基礎となる機能を担う細胞内小器官である。そのため、ER機能の破綻は、蛋白質輸送の阻害に加え、代謝や脂質合成などを変化させ、結果的に種々な疾患を引き起こす。ADAMTS9の細胞内機能を明らかにし、蛋白質輸送の恒常性を保つメカニズムと、を解明することにより、広い生命科学分野の理解と、病態の解明につながることが期待される。
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