Elucidation of sensing mechanism of lipid asymmetry and establishment of bases for its application
| Project/Area Number |
16K07288
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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 |
Functional biochemistry
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| Research Institution | Nagoya University (2017-2019)
Hokkaido University (2016) |
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Principal Investigator |
Obara Keisuke 名古屋大学, 理学研究科, 助教 (30419858)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脂質非対称 / 細胞膜 / 出芽酵母 / バイオセンサー / 真菌感染症 / ストレス応答 / 酵母 / タンパク質分解 / センサー / 脂質 / センシング / Rim101 |
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| Outline of Final Research Achievements |
In this study, we focused on Rim21, the sensor protein for altered lipid asymmetry in the plasma membrane. We suggested that Rim21 senses alterations in lipid asymmetry through interaction between lipid asymmetry sensor motifs in Rim21 and acidic lipids in the plasma membrane. We also elucidated the function of N-glycosylation of Rim21.
A biosensor that can report the state of lipid asymmetry in living yeast cells was developed in this study. Moreover, we succeeded in improving the S/N ratio of this prototype biosensor by mutagenesis approach.
Rim21 invokes a signal transduction pathway called the Rim101 pathway, and this pathway is a good potential drug target. We revealed that activation of this pathway is regulated by antagonistic action of ubiquitination and deubiquitination. In addition, we elucidated the mechanism and the biological significance of attenuation of the Rim101 pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で行ったRim21による脂質非対称感知機構に関する提案は、タンパク質と脂質の相互作用に関する新たなパラダイムと成り得る。
本研究で開発した脂質非対称バイオセンサーは、生きた細胞での脂質非対称変化の追跡という、これまで不可能であったアプローチを可能とする。今後、動植物細胞で利用可能なバイオセンサーの開発などを通して、脂質非対称研究のボトルネックであった生細胞でのリアルタイム解析を達成し、分野の発展に大きく貢献する可能性がある。
本研究で明らかにしたRim101経路の不活性化機構は、真菌感染症の創薬に寄与する知見となる。
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Report
(5 results)
Research Products
(14 results)
