Sphingolipid-dependent mechanisms of TOR kinase complex I regulation
| Project/Area Number |
16K07693
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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 |
Applied biochemistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
FUNATO KOUICHI 広島大学, 生物圏科学研究科, 准教授 (30379854)
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| Co-Investigator(Kenkyū-buntansha) |
田淵 光昭 香川大学, 農学部, 教授 (00294637)
田中 直孝 香川大学, 農学部, 准教授 (60324109)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | スフィンゴ脂質 / TOR複合体1 / TOR複合体2 / EGO複合体 / 酵母 / TORC1 / 液胞膜 / ドメイン / ステロール / TORC2 / Ypk1/2 / ORM1/2 / Gtr1 / TORキナーゼ / 脂質 |
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| Outline of Final Research Achievements |
TOR (target of rapamycin) complex I is a highly conserved protein kinase complex that functions as a nutrient/stress-sensitive, central controller of cell growth and aging. In this study, using yeast mutant strains and approach to localize proteins artificially, we found that sphingolipids regulate TORC1 though the upstream regulator EGO complex. In addition, our data suggested that sphingolipid-mediated TORC1 regulation is tightly linked to the TORC2 signaling pathway and the structure and function of vacuoles.
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| Academic Significance and Societal Importance of the Research Achievements |
老化，寿命，癌，肥満などの疾患に関与する主要シグナル分子TOR（Target of Rapamycin) の活性は，栄養源やストレスなど多様なシグナルにより制御されるが，その制御機構は不明な点が多い。本研究で，生体膜の主要成分であるスフィンゴ脂質がTORC1の上流で機能するタンパク質複合体の制御を介してTORC1を調節していることが明らかになった。また，スフィンゴ脂質によるTORC1の調節には，構成因子と機能が異なる別のTOR複合体2（TORC2）を介したシグナル経路も深く関わっていることも明らかとなり，TORC1の制御機構およびTOR複合体間の機能連携の理解の進展に貢献した。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy2016
Author(s)
Palmer EE, Jarrett KE, Sachdev RK, Al Zahrani F, Hashem MO, Ibrahim N, Sampaio H, Kandula T, Macintosh R, Gupta R, Conlon DM, Billheimer JT, Rader DJ, Funato K, Walkey CJ, Lee CS, Loo C, Brammah S, Elakis G, Zhu Y, Buckley M, Kirk EP, Bye A, Alkuraya FS, Roscioli T, Lagor WR.
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Journal Title
Hum. Mol. Genet.
Volume: 25
Pages: 3042-3054
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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