Functional analysis of peroxisomal membrane translocator
| Project/Area Number |
16K07275
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
藤木 幸夫 九州大学, 生体防御医学研究所, 特任教授 (70261237)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ペルオキシソーム / 膜透過輸送 / 病因変異解析 / リン酸化 / ペルオキシソーム欠損症 / 病因解析 / タンパク質輸送 / 複合体形成 / タンパク質相互作用 / ペルオキシソーム形成因子 / 細胞内小器官 / タンパク質複合体 / 恒常性維持 |
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| Outline of Final Research Achievements |
Peroxisomal matrix proteins are imported into peroxisomes via membrane-bound docking/translocation complex comprising as a major component membrane peroxin Pex14p that binds Pex5p. In this study, we isolated three types of Pex14p complexes, termed complexes I, II, and III, as a docking/translocation complex. Transition of Pex14p complex structures between complexes I, II, and III more likely plays important roles in matrix protein import.
Next, using clinical exome sequencing (ES), we identified an autosomal recessive missense variant, c.153C>A (p.F51L), in the peroxisome biogenesis factor 26 gene (PEX26) in a 19-yr-old female who was referred for moderate to severe hearing loss. The functional data of Pex26p support the mild phenotype of non-syndromic hearing loss in patients harboring the F51L variant in PEX26.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題研究にてペルオキシソーム膜透過輸送装置を同定し、リン酸化による機能制御システムを明らかにしたことで、その生合成機構の全容解明に向けた分子レベルでの手がかりを得ることができた。また、PEX26の病因変異解析から、ペルオキシソーム代謝障害と聴覚障害の相関を明らかにした。つまり、タンパク質の細胞内選別輸送やオルガネラ形成とその恒常性維持などプロテインキネシスにおける課題解明だけでなく、中枢神経系の中でもとくに聴覚神経細胞の発達と維持のメカニズム解明など医学領域への多大な貢献が期待できる。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] A newly identified mutation in the PEX26 gene is associated with a milder form of Zellweger spectrum disorder.2019
Author(s)
Tanaka, A. J., Okumoto, K., Tamura, S., Abe, Y., Hirsch, Y., Deng, L., Ekstein, J., Chung, W. K., and Fujiki Y.
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Journal Title
Cold Spring Harb. Mol. Case Stud.
Volume: 5
Issue: 1
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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