| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Hirano Yoshinori (日) (読)
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| 2. | (英) Amano Yu (日) (読)
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| 3. | 米村 重信 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.細胞生物学])
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| 4. | (英) Takoshima Toshio (日) (読)
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| ○題名 (必須): | □ | (英) The force-sensing device region of alpha-catenin in an intrinsically disordered segment in the absence of intramolecular stabilization of the auto inhibitory form. (日)
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| ○要約 (任意): | □ | (英) Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G. Our molecular dissection study showed that helix bundles F and G are stable in solution in each isolated form, whereas helix bundle E that contains VBS1 is unstable and intrinsically disordered in solution in the isolated form. We successfully identified key residues mediating the autoinhibition and produced mutated α-catenins that display variable force sensitivity and autoinhibition. Using these mutants, we demonstrate both in vitro and in vivo that, in the absence of this stabilization, the helix bundle containing VBS1 would adopt an unfolded form, thus exposing VBS for vinculin binding. We provide evidence for importance of mechanotransduction with the intrinsic force sensitivity for vinculin recruitment to adherens junctions of epithelial cell sheets with mutated α-catenins. (日)
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| ○キーワード (推奨): | 1. | (英) Actins (日) (読)
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| 2. | (英) Adherens Junctions (日) (読)
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| 3. | (英) Animals (日) (読)
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| 4. | (英) Binding Sites (日) (読)
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| 5. | (英) Crystallography, X-Ray (日) (読)
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| 6. | (英) Mechanotransduction, Cellular (日) (読)
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| 7. | (英) Mice (日) (読)
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| 8. | (英) Models, Molecular (日) (読)
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| 9. | (英) Mutation (日) (読)
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| 10. | (英) Protein Binding (日) (読)
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| 11. | (英) Protein Conformation (日) (読)
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| 12. | (英) Protein Folding (日) (読)
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| 13. | (英) Vinculin (日) (読)
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| 14. | (英) alpha Catenin (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Genes to Cells ([日本分子生物学会])
(pISSN: 1356-9597, eISSN: 1365-2443)
| ○ISSN (任意): | □ | 1365-2443
ISSN: 1356-9597
(pISSN: 1356-9597, eISSN: 1365-2443) Title: Genes to cells : devoted to molecular & cellular mechanismsTitle(ISO): Genes CellsSupplier: Molecular Biology Society of JapanPublisher: Wiley Publishing (NLM Catalog)
(Wiley)
(Scopus)
(CrossRef)
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| ○巻 (必須): | □ | 23
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| ○号 (必須): | □ | 5
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| ○頁 (必須): | □ | 370 385
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2018年 3月 15日 (平成 30年 3月 15日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1111/gtc.12578 (→Scopusで検索)
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| ○PMID (任意): | □ | 29542234 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1111/gtc.12578 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) KeywordList.Keyword: X-ray crystallography (日)
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| 4. | (英) KeywordList.Keyword: adherens junction (日)
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| 5. | (英) KeywordList.Keyword: cytoskeletal tension (日)
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| 6. | (英) KeywordList.Keyword: mechanotransduction (日)
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| 7. | (英) KeywordList.Keyword: vinculin (日)
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| 8. | (英) KeywordList.Keyword: α-catenin (日)
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