| Project/Area Number |
18K19292
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | Nagoya University |
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Principal Investigator |
Kamura Takumi 名古屋大学, 理学研究科, 教授 (40333455)
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| Co-Investigator(Kenkyū-buntansha) |
小原 圭介 名古屋大学, 理学研究科, 助教 (30419858)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 脂質非対称 / 細胞膜 / バイオセンサー / 生体膜、 / ストレス / 出芽酵母 / GFP / 膜動態 |
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| Outline of Final Research Achievements |
In this study, we tried to develop a biosensor that can report the state of lipid asymmetry in the plasma membrane. For this purpose, we focused on and utilized a lipid asymmetry sensor protein Rim21 which we previously identified in yeast. As a result, we developed a prototype of lipid asymmetry biosensor that can visualize alterations in lipid asymmetry in living yeast cells. In addition, we conducted a systematic mutagenesis approach of the prototype biosensor, and succeeded in developing a series of improved biosensors with higher S/N ratio.
Using these biosensors, we monitored the state of lipid asymmetry in yeast cells exposed to environmental stresses. Interestingly, the state of lipid symmetry seemed to be altered under alkaline and salt stresses. Cells deleted for RIM21 were hypersensitive to alkaline and salt stresses, suggesting that these environmental stresses are sensed by Rim21 through alterations in the state of lipid asymmetry in the plasma membrane.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で開発した脂質非対称バイオセンサーは遺伝子にコードされているため、増幅、保存、輸送などが簡便である。国内外の研究者のリクエストに応じることで、生体膜研究の分野に大きく貢献できる。
また、本研究では細胞外のpHや塩濃度などの物理化学変数の幾つかが、脂質非対称など細胞膜の物理化学的状態に変化をもたらし、その変化を細胞膜に存在するセンサータンパク質群が感知することを示唆した。細胞外の物理化学変数を細胞が感知する仕組みはほとんど明らかになっていないが、この様な新たな概念は、細胞のストレス受容機構の研究に大きなパラダイムシフトを起こす可能性を秘めている。
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