Mechanisms of phospholipid scrambling on plasma membranes by Xkr8
| Project/Area Number |
15H05651
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto University (2017-2018)
Osaka University (2015-2016) |
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Principal Investigator |
Suzuki Jun 京都大学, 高等研究院, 教授 (30511894)
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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 |
¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | ホスファチジルセリン / 貪食 / スクランブラーゼ / Xkr8 / カスパーゼ / ダイマー / サブユニット / Xkrファミリー / アポトーシス / CRISPR / スクリーニング / シャペロン / Xkr / リン脂質 / Basigin / Neuroplastin / Ｘｋｒ８ / 複合体 |
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| Outline of Final Research Achievements |
In this study, I investigated the mechanisms of phosphatidylserine (PS) exposure during apoptotsis by Xkr8 and its family memebrs. As a result, i found that Xkr8 is cleaved at its C-temrinal region of Caspase3, which results in dimerization of the molecules to be activated. the subunit analysis of Xkr8 identified BSG and NPTN as binding partners of Xkr8. Without binding to them, Xkr8 cannot reach to the plasma membrane, indicating that they function as chaperones to take Xkr8 to the plasma membrane. I also found that other Xkr family members are not dependent on BSG or NPTN to localize to the plasma membrane, suggesting that other chapernes are required for for other family memebrs. Finally, the screening system to discover the chaperones were established.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞がアポトーシスによって死んだ時には、"Eat-me signal"としてホスファチジルセリン（PS）を細胞表面に露出することでマクロファージ等の食細胞に貪食されることが知られている。本研究はPSを露出するXkr8について解析し、Xkr8がどのように活性化してPSが露出されるのかを明らかにした。これにより今後この過程を薬剤等で制御することで、生体にとって不必要なものを貪食させることができるかもしれない。
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Report
(5 results)
Research Products
(40 results)
