Mechanisms of growth arrest-induced primary cilium formation
| Project/Area Number |
18H02398
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Mizuno Kensaku 東北大学, 生命科学研究科, 名誉教授 (70128396)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 一次繊毛 / ユビキチン化 / ユビキチンリガーゼ / 繊毛病 / CEP97 / CEP104 / ヘッジホッグ / YAP / 繊毛 / 細胞増殖 / 微小管 / 中心体 / Hedgehog / 細胞周期 |
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| Outline of Final Research Achievements |
Primary cilia are antenna-like sensory organelles that transmit various extracellular signals. Deficits in ciliogenesis cause human disorders that are termed ciliopathies. In this project, we aimed to elucidate the mechanisms of growth arrest signal-induced ciliogenesis and obtained several findings as follows: 1) Ciliogenesis requires the removal of CEP97 from the mother centriole for initiating ciliary axoneme extension. We showed that CEP97 is degraded by the cullin-3-RBX1-KCTD10 ubiquitin ligase complex and this process is crucial for serum starvation-induced ciliogenesis. 2) CEP104 is a causative gene for Joubert syndrome. We showed that the TOG domain of CEP104 exhibits microtubule-polymerizing activity and this activity is essential for growth arrest-induced cilium elongation and Hedgehog signaling. 3) We showed that Furry suppresses nuclear localization of YAP by activating NDR1/2 kinases and directly binding to YAP.
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| Academic Significance and Societal Importance of the Research Achievements |
一次繊毛は、多くの動物細胞が有する非運動性の繊毛で、ヘッジホッグなどの多様なシグナルを受容するアンテナとして、細胞の増殖・分化や組織の形成・恒常性維持に重要な役割を担っている。一次繊毛の形成不全は嚢胞腎、網膜変性など繊毛病とよばれる多様な疾患の原因となることが知られており、一次繊毛形成機構の解明は発生学的にも医学的にも重要な課題である。本研究では、一次繊毛形成の初期過程で重要な役割を担っているCEP97の分解機構とCEP104の微小管制御機構について新たな知見を得た。これらの成果は、一次繊毛形成の重要な機構を解明したものであり、基礎生物学の進展だけでなく医学分野にも貢献すると考えられる。
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Report
(4 results)
Research Products
(9 results)
