Actin cytoskeletal regulation of process formation in kidney podocytes.
| Project/Area Number |
18K06227
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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 44010:Cell biology-related
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| Research Institution | Kitasato University |
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Principal Investigator |
Saito Koji 北里大学, 理学部, 講師 (70556901)
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| Co-Investigator(Kenkyū-buntansha) |
太田 安隆 北里大学, 理学部, 教授 (90192517)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腎ポドサイト / 突起構造 / 細胞骨格 / Rho small GTPase / ポドサイト細胞株 / ポドサイト / Rac / FilGAP / PAK / cAMPシグナル / Epac / PI3K/PIP3 / cAMP / Rap1 / PIP3 / ROCK / 腎糸球体上皮細胞 / アクチン細胞骨格 |
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| Outline of Final Research Achievements |
Kidney podocytes, which are essential for glomerular filtration barrier maintenance, have highly developed process structures supported by an actin cytoskeleton. Using in vitro experiments with an unique podocyte cell line capable of inducing the formation of highly organized cell processes, we identified FilGAP, a GTPase-activating protein (GAP) for Rho small GTPase Rac1, as an important regulator that mediates the formation of processes in podocytes. In this study, we found that the inactivation of Rac1 by FilGAP is required for the process formation of podocytes. Moreover, FilGAP regulated the process formation through suppression of P21-activated kinase 1 (PAK1), a downstream effector of Rac1. Finally, we propose that FilGAP, as a Rac1 GAP, contributes to the process formation of podocytes by suppressing Rac1/PAK1 signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
ポドサイトの突起消失を特徴とするポドサイト障害では、大量の蛋白尿を呈する腎疾患が生じる。ポドサイト障害を要因とする進行性の腎疾患は、最終的に腎不全に至るケースもあり、医学的観点からその発症に関わる分子機構の解明が望まれている。本研究ではin vitro実験による解析から、ポドサイトの突起形成に関わる分子の一つとして、Rac1 GAPであるFilGAPを同定した。本研究で得られたポドサイトの突起形成に関わる分子機構の知見は、今後の生体を用いた解析(遺伝子欠損マウスなど)に活かされ、最終的に、ポドサイト障害(突起消失)を通じた腎疾患発症の作用機序の解明につながると期待できる。
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Report
(5 results)
Research Products
(12 results)
