| Project/Area Number |
24370056
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
OGURA Teru 熊本大学, 発生医学研究所, 教授 (00158825)
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| Co-Investigator(Renkei-kenkyūsha) |
OKUNO Takashi 山形大学, 理学部, 准教授 (80411031)
YAMANAKA Kunitoshi 熊本大学, 発生医学研究所, 准教授 (90212290)
ESAKI Masatoshi 熊本大学, 発生医学研究所, 助教 (70437911)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | AAAタンパク質 / 分子シャペロン / プロテアソーム / p97/VCP/CDC-48/Cdc48 / Katanin / 高速原子間力顕微鏡 / ミトコンドリア / 微小管 / katanin / p97/CDC-48/Cdc48 / ポリグルタミン凝集体 / 26Sプロテアソーム / 神経変性疾患 |
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| Outline of Final Research Achievements |
AAA family chaperones/proteases form a hexameric ring structure. ATP-dependent rotation of the AAA chaperone p97 was analyzed by high-speed AFM, and a novel model for the p97 action against substrate has been proposed. It has been found that VCP, a human p97 homolog, binds to amyloid fibrils of TDP-43. UFD-3 is an adapter of CDC-48, a C. elegans p97 homolog, and has been revealed to regulate polyglutamine aggregate formation. Abnormal mitochondrial morphology caused by a mutation of Cdc48, a yeast p97 homolog, was precisely analyzed by advanced microscopic techniques. Dynamics of the 26S proteasome and its complex with a substrate were analyzed by high-speed AFM. Microtubule severing by katanin was analyzed, and a novel model for the mechanism of katanin has been proposed. Functional importance of mitochondrial Bcs1 was revealed.
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