| Project/Area Number |
17K07397
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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 |
Cell biology
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| Research Institution | Waseda University |
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Principal Investigator |
TOYA Mika 早稲田大学, 理工学術院, 准教授(任期付) (80455360)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 上皮細胞 / 微小管編成 / 腎臓 / 嚢胞腎 / 微小管マイナス端 / 非中心体微小管 / CAMSAP3 / ノックアウトマウス / CAMSAP3/Nezha / 腎嚢胞 / 細胞・組織 / 微小管 / 腎尿細管 |
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| Outline of Final Research Achievements |
Epithelial cells organize a characteristic, an ordered, array of non-centrosomal microtubules. CAMSAP3, a microtubule minus-end binding protein, orients the microtubules, however, their role in epithelial functions are not fully understood. We analyzed Camsap3 mutant mice and found that they show a polycystic kidney disease-like phenotype. The blood K+ or Mg++ level was significantly lower in the mutant mice. Further analysis revealed that the proximal convoluted tubules (PCTs) were specifically dilated. The epithelial cells at the dilated PCTs became stretched, and they contained disorganized microtubules. Cell proliferation was promoted in the PCTs cells along with activation of mechanosensitive regulators. These observations suggest that the epithelial array of microtubules is important for the integrity of PCTs, and lack of this assembly causes cell stretching, leading activation of mechanosensitive regulators and cell proliferation, resulting in cystic tubular dilation.
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| Academic Significance and Societal Importance of the Research Achievements |
多くの臓器を構成する上皮細胞で、微小管は、その特徴的な編成から上皮機能に重要な役割をもつと考えられてきた。しかしながら、その生理的な役割は未だ不明な点が多い。本研究において、上皮微小管編成が、腎臓の構造と機能に重要であることを明らかにし、また、嚢胞腎形成の新たな機構を示唆することができた。基礎生物学、基礎医学に貢献する成果が得られたと考える。
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