Actin cytoskelton regulation in the inner ear
| 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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Report
(5 results)
Research Products
(34 results)
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[Journal Article] Constitutive activation of DIA1 (DIAPH1) via C-terminal truncation causes human sensorineural hearing loss.2016
Author(s)
Ueyama T, Ninoyu Y, Nishio S, Miyoshi T, Torii H, Nishimura K, Sugahara K, Sakata H, Thumkeo D, Sakaguchi H, Watanabe N, Usami S, Saito N, Kitajiri S.
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Journal Title
EMBO Molecular Medicine
Volume: 8
Issue: 11
Pages: 1310-1324
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] TRIOBP5 Deficient Mouse is Deaf But Hair Cells Develop Stereocilia Rootlets2017
Author(s)
Inna A. Belyantseva, Tatsuya Katsuno, Gavin Riordan, Atteeq Rehman, Ayesha Imtiaz, Erich Boger, Eva Morozko, Joesh Duda, Elizabeth Wilson, Tracy Fitzgerald, Thomas B Friedman, Shin-ichiro Kitajiri
Organizer
ARO The 40th Annual MidWinter Meeting
Related Report
Int'l Joint Research
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[Presentation] The development and maintenance of hair cell stereocilia rootlets by isoform specific functions of TRIOBP2017
Author(s)
Tatsuya Katsuno, Inna A. Belyantseva, Ronald S. Petralia, Ya-Xian Wang, Keisuke Ohta, Kazuya Ono, Makoto Ikeya, Gavin P. Riordan, Joseph Duda, Elizabeth Wilson, Tracy Fitzgerald, Atteeq U. Rehman, Ayesha Imtiaz, Juichi Ito, Thomas B. Friedman, Shin-ichiro Kitajiri
Organizer
54th workshop on Inner Ear Biology and Symposium
Related Report
Int'l Joint Research
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[Presentation] Characteristics of the Genetic Counseling in Kyoto University Hospital to Figure out the Genetic Counseling Needs in Japan2016
Author(s)
Manami Matsunaga, Hitomi Nishio, Yumie Hiraoka, Sayaka Honda, Akira Inaba, Eriko Takamine, Ayumi Yonei, Masako Torishima, Hiromi Murakami, Shin-ichiro Kitajiri, Takahiko Wada, Hidehiko Miyake, Shigehito Yamada, Toshio Heike, Shinji Kosugi
Organizer
The 13th Interntional Congress of Human Genetics
Place of Presentation
Kyoto International Conference Center
Year and Date
2016-04-03
Related Report
Int'l Joint Research
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