| Project/Area Number |
17H05057
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | University of Yamanashi |
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Principal Investigator |
ODA TOSHIYUKI 山梨大学, 大学院総合研究部, 教授 (20569090)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2018: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2017: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
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| Keywords | 繊毛 / モータータンパク質 / クライオ電子顕微鏡 / 微小管 / 細胞骨格 / 繊毛・鞭毛 / 翻訳後修飾 / ダイニン / 電子顕微鏡 / 三次元構造解析 |
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| Outline of Final Research Achievements |
Cilium is a conserved motile organelles and plays essential roles in cellular motility, airway clearance, and cerebrospinal fluid circulation. Below are the major findings in our study:
1. We investigated the function of a post-translational modification of ciliary tubulin using genetics and cryo-electron tomography. We revealed that tubulin poly-glutamylation occurs at specific sites on the ciliary microtubules and the negative charges applied to the positions are essential for normal ciliary motility.
2. We analyzed the function of novel ciliary proteins: FAP43, FAP44, FAP244, and FAP70. We found that FAP43, FAP44 and FAP244 form a "tethering" complex, which connects the inner dynein f to the microtubule. We also found that FAP70 is a novel regulatory subunit for the outer dynein arm.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究により、人体において重要な役割を果たしている繊毛の運動を制御している新しい分子メカニズムが明らかになった。繊毛の機能不全は、胎児期の発生異常や慢性気道感染症、水頭症、不妊などの様々な疾患に関わっている。今回の研究はこれらの繊毛関連疾患の病態理解を深め、疾患の治療の進歩に貢献することが期待される。またチューブリンの修飾に関する発見は繊毛だけでなく、細胞骨格に関わる広範な細胞生物学の理解に貢献した。
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