| Project/Area Number |
20390439
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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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| Research Field |
Otorhinolaryngology
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| Research Institution | Tohoku University |
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Principal Investigator |
WADA Hiroshi Tohoku University, 大学院・工学研究科, 教授 (30111264)
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| Co-Investigator(Kenkyū-buntansha) |
USAMI Shinichi 信州大学, 医学部, 教授 (10184996)
ISHIHARA Kenji 茨城大学, 教育学部, 准教授 (00312596)
村越 道生 東北大学, 大学院・工学研究科, 助教 (70570901)
小山 眞 東北大学, 大学院・工学研究科, 助教 (10465487)
浜名 洋 東北大学, 大学院・工学研究科, 助教 (90551549)
飯田 浩司 東北大学, 大学院・工学研究科, 助教 (00451534)
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| Co-Investigator(Renkei-kenkyūsha) |
KOBAYASHI Toshimitsu 東北大学, 大学院・医学系研究科, 教授 (80133958)
KUMAGAI Izumi 東北大学, 大学院・工学研究科, 教授 (10161689)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2008: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | 耳科学 / 遺伝性難聴 / ペンドリン / タンパク質フォールディング / Pendrin |
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| Research Abstract |
The SLC26A4 gene encodes the transmembrane protein pendrin, which is involved in the conditioning of the ion concentration in the endolymph of the inner ear. Mutations in the SLC26A4 gene cause sensorineuronal hearing loss. However, the mechanisms responsible for such loss have remained unknown. In this study, therefore, cellular localization and anion exchanger activity were analyzed by using HEK293 cells transfected with mutant genes. First, 10 pendrin mutants reported in Japanese patients were constructed. Immunofluorescent staining of the cellular localization of the pendrin mutants revealed that normal pendrin was transported to the plasma membrane ; however, 8 mutants were retained in the cytoplasm. Furthermore, we analyzed whether salicylate, as a pharmacological chaperone, restored the function. Incubation with 10 mM of salicylate of the cells transfected with the mutants induced the transport of 4 pendrin mutants from the cytoplasm to the plasma membrane and recovered the anion exchanger activity.
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