2019 Fiscal Year Final Research Report
Physiological roles of Phosphoinositide-specific phosphatase in lung development and maturation through regulating membrane trafficking.
| Project/Area Number |
17K08532
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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 |
General physiology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | ホスホイノシタイド / 脂質ホスファターゼ / ミオチュブラリン関連タンパク質 / PI3キナーゼ / エンドサイトーシス / オートファジー / リソソーム / II型肺胞上皮細胞 |
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| Outline of Final Research Achievements |
Phosphatidylinositol 3-phosphate (PI(3)P) is the predominant phosphoinositide species in early endosomes and autophagosomes, in which PI(3)P dictates traffic of these organelles. Phosphoinositide levels are tightly regulated by lipid-kinases and-phosphatases; however, a phosphatase that converts PI(3)P back to phosphatidylinositol in the endosomal and autophagosomal compartments is not fully understood. We investigated the subcellular distribution and functions of myotubularin-related protein-4 (MTMR4), which is distinct among other MTMRs in that it possesses a PI(3)P-binding FYVE domain, in lung alveolar epithelial cells. MTMR4 knockdown markedly suppressed the motility, fusion, and fission of PI(3)P-enriched structures, resulting in decreases in late endosomes, autophagosomes, and lysosomes. This project has unveiled that MTMR4 is essential for the integrity of endocytic and autophagic pathways.
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| Free Research Field |
生理学
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| Academic Significance and Societal Importance of the Research Achievements |
サーファクタントを分泌するII型肺胞上皮（AECII）細胞は正常肺発生において肺胞を形成する組織幹細胞であり、また外部環境由来の病原体アラームシグナルをいち早く感知し、これらによる肺組織の障害に対する防御・修復応答に中心的な役割をはたすことが明らかになってきた。本研究の成果は、MTMR4がAECII細胞の細胞内クリアランス制御を介して細胞分化・増殖を調整して肺組織の構築および恒常性を維持する機能を有することを示した。この研究成果は肺形成・発達メカニズムの解明のみならず、肺線維症等の炎症性肺疾患（全世界の死亡原因第３）の病態解明と新しい治療法開発戦略において有用な情報を与える。
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