2018 Fiscal Year Final Research Report
The role of cellular localization of ALOX proteins in vascular aging
| Project/Area Number |
15K09451
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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 |
Hematology
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| Research Institution | National Center for Geriatrics and Gerontology (2016-2018)
Hamamatsu University School of Medicine (2015) |
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Principal Investigator |
KATSUMI Akira 国立研究開発法人国立長寿医療研究センター, 病院, 部長 (80378025)
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| Co-Investigator(Kenkyū-buntansha) |
丸山 光生 国立研究開発法人国立長寿医療研究センター, その他部局等, 副所長 (00212225)
天野 睦紀 名古屋大学, 医学系研究科, 准教授 (90304170)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | RhoA / 脂質メディエーター / 細胞内輸送 |
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| Outline of Final Research Achievements |
Rho family proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.To identify novel downstream effectors of RhoA, we performed GST-RhoA affinity column chromatography by using platelet lysates. Cytosol fraction of platelet was loaded onto affinity columns on which GST, GST-RhoA-N19, or GST-RhoA-L63 was immobilized. Using triple quadrupole liquid chromatography tandem mass spectrometer, several proteins associated with active RhoA were identified. Arachidonate lipoxygenase (ALOX) binds to GST-RhoA-L63, but not to GST-RhoA-N19 along with the known RhoA effectors. ALOX does not directly bind to RhoA-L63, although Daam1 is shown to bind to ALOX. The second LH2 domain of ALOX directly binds to N-terminal of Daam1, suggesting that Daam1 functions as a scaffolding protein for the assembly of ALOX. We further investigate the roles of Daam1 on ALOX activity and subcellular localization of these molecules.
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| Free Research Field |
血液内科
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| Academic Significance and Societal Importance of the Research Achievements |
アラキドン酸リポキシゲナーゼ(ALOX)とその下流の脂質メディエーターは動脈硬化、血小板凝集、慢性炎症、がんの進展などに関与する多機能蛋白である。ALOX下流の脂質メディエーターについては活発に研究が行われているが、上流の制御メカニズムについては殆ど報告がなされていなかった。当該研究ではLOXの細胞内局在をRho family GTPaseが制御しており、動脈硬化部位、免疫器官など多様な臓器に脂質メディエーターをリクルートする際にこの経路が重要であるという新たな知見を得た。
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