| Project/Area Number |
26293369
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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 |
Otorhinolaryngology
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| Research Institution | Shinshu University (2017)
Kyoto University (2014-2016) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 壽一 京都大学, 医学研究科, 名誉教授 (90176339)
Raj Ladher (RAJ Ladher) 国立研究開発法人理化学研究所, 発生・再生科学総合研究センター, 特別主管研究員 (70392173)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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| Keywords | アクチン / 不動毛 / 根 / 聴力 / TRIOBP / リン酸化 / MYPT / 加齢性難聴 / 聴覚 / 剛性 / プルダウン |
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| Outline of Final Research Achievements |
Mice lacking both TRIOBP-4 and TRIOBP-5 are profoundly congenitally deaf by loss of rootlets. In transgenic Triobp-4GFP mice, GFP-TRIOBP-4 localizes to rootlet segments within stereocilia. TRIOBP-5 homo-multimerizes and concentrates in rootlet segments embedded in the cuticular plate. Strikingly, TRIOBP-5 specific deficient mutants (TRIOBP-5 KO) show progressive hearing loss and develop dysmorphic, fragile stereocilia rootlets. During fluid-jet stimulation of increasing intensity, Triobp-5 KO stereocilia bundles of hair cells show increased pivotal-flexibility and susceptibility to damage. Atomic Force Microscopy detected a two-fold decreased apical surface stiffness in live TRIOBP-5 KO supporting cells. Thus, stereocilia rootlet formation requires TRIOBP-4, while TRIOBP-5 reinforces rootlets for life-long acoustical stimulation and also provides force-homeostasis across the sensory epithelium.
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