| Project/Area Number |
25840065
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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 |
Cell biology
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| Research Institution | Osaka University |
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Principal Investigator |
CHIBA Shuhei 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (60572493)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 一次繊毛 / 細胞周期 / NDR / Rabin8 / Hippo / 基底小体 / 繊毛症 / Rab8 / Distal Appendages / 増殖と分化 / 膜輸送 / Hippo経路 / 中心体サイクル / 繊毛鞘 |
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| Outline of Final Research Achievements |
NDR2, an effector molecule for mammalian Hippo signalling, was identified as the causal gene for a canine ciliopathy, early retinal degeneration. Little is known how NDR2 regulates cilium formation. Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome, a process requiring Rab11-mediated recruitment of Rabin8, subsequent activation of Rab8 and Rabin8 binding to Sec15. I found that NDR2 phosphorylates Rabin8 and defects in this phosphorylation impair preciliary membrane assembly and ciliogenesis. NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by triggering the switch in binding specificity of Rabin8 from PS to Sec15, thereby promoting local activation of Rab8 and ciliary membrane formation. Additionally, I identified a certain member of lipid kinase as a new physiological substrate for NDR2. These results suggest that the NDR2 is crucial for ciliogenesis by regulating intracellular vesicle trafficking.
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