| Project/Area Number |
18K06934
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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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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 細胞極性 / タイトジャンクション / 上皮細胞 |
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| Outline of Final Research Achievements |
The evolutionarily conserved polarity regulator Par3 is known to promote TJ formation during epithelial cell polarization. However, the mechanism for Par3-mediated TJ formation has not been fully understood. Here, we have identified the transmembrane protein ParTR1 as a novel Par3-binding protein that localizes to TJs. During polarization of Madin-Darby canine kidney epithelial cells, ParTR1 negatively regulates TJ formation; the development of TJs is delayed by over-expression of ParTR1 and is conversely accelerated by its knockdown. ParTR1 interacts with the tetra-span transmembrane protein claudins, major constituents of TJ strands, to inhibit their functions. Meanwhile, Par3 prevents the ParTR1-claudin interaction in a manner dependent on its ability to associate with ParTR1. Thus, Par3 appears to promote TJ formation at least in part by suppressing ParTR1, a newly identified negative regulator of claudins.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、国内外の研究において長年不明であった「細胞極性蛋白質がどのようにTJを形成させるのか」という問いに対して、少なくとも部分的に答えを与え得るものと考えている。TJ に関連するこれまでの研究において、claudin分子のオリゴマー化に対する負の制御因子の報告は極めて珍しく、この新規TJ 制御因子の報告はインパクトを与えることが期待される。また、この制御因子がTJに特異的に局在する膜タンパク質であることからTJをターゲットとした創薬や薬物デリバリーの候補や、上皮に関連した疾患の理解や治療法の基礎を提供し得るかもしれない。
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