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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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | RhoA / 脂質メディエーター / 細胞内輸送 / Rho / フォルミン / リポキシゲナーゼ / Rho GTPase / エフェクター / 血管老化 / Rhoファミリー / アラキドン酸リポキシゲナーゼ |
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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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| 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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Report
(5 results)
Research Products
(21 results)
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[Journal Article] Apparent synonymous mutation F9 c.87A>G causes secretion failure by in-frame mutation with aberrant splicing.2019
Author(s)
Odaira K, Tamura S, Suzuki, N Kakihara M, Hattori Y, Tokoro M, Suzuki S, Takagi A, Katsumi A, Hayakawa F, Okamoto S, Suzuki A, Kanematsu T, Matsushita T, Kojima T.
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Journal Title
Thrombosis Research
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1-RUNX1T1 leukemia with t(8;12;21).2017
Author(s)
Abe A, Yamamoto Y, Katsumi A, Okamoto A, Tokuda M, Inaguma Y, Yamamoto K, Yanada M, Kanie T, Tomita A, Akatsuka Y, Okamoto M, Kameyama T, Mayeda A, Emi N.
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Journal Title
Int J Hematol.
Volume: -
Issue: 2
Pages: 208-212
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Efficacy of Eculizumab for aplastic anemia developed to paroximal nocturnal hemogrobinuria after IST2018
Author(s)
Seara Ikeno, Motohito Okabe, Yuka Kawaguchi, Marie Ohbiki, Yoonha Lee, Masahide Osaki, Miyo Goto, Hiroaki Araie, Takahiko Sato, Takanobu Morishita, Yukiyasu Ozawa, Akira Katsumi, Koichi Miyamura
Organizer
第80回日本血液学会学術集会
Related Report
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[Presentation] Arachidonate 12-lipoxygenase binds to active RhoA through Daam12017
Author(s)
Moe Murata, Akira Katsumi, Katsuhiro Kato, Asami Matsuda, Tomoki Nishioka, Mutsuki Amano, Tadashi Matsushita, Hitoshi Kiyoi, Mitsuo Maruyama, Tetsuhito Kojima, Kozo Kaibuchi
Organizer
第39回日本血栓止血学会学術集会
Related Report
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[Presentation] Arachidonate 12-lipoxygenase binds to active RhoA through Daam12017
Author(s)
Moe Murata, Akira Katsumi, Katsuhiro Kato, Asami Matsuda, Tomoki Nishioka, Mutsuki Amano, Tadashi Matsushita, Hitoshi Kiyoi, Mitsuo Maruyama, Tetsuhito Kojima, Kozo Kaibuchi
Organizer
第79回日本血液学会学術集会
Related Report
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[Presentation] Rho H, a hematopoietic cell specific Rho protein, Deactivates Rac through T cell activation GTPase activating protein (TAGAP)2015
Author(s)
Asami Matsuda , Akira Katsumi , Mutsuki Amano , Yasuyuki Nagata , Takaaki Ono , Mitsuo Maruyama , Hiroshi Kiyoi, Tomoki Naoe, Kozo Kaibuchi
Organizer
第38回日本分子生物学会年会
Place of Presentation
神戸ポートアイランド
Year and Date
2015-12-01
Related Report
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