| Project/Area Number |
18K14698
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 脂肪酸伸長酵素 / 小胞体 / カルシウム / カルシウムシグナル / SERCA / NFAT / 脂肪酸 / 脂質代謝 / 膜変形タンパク質 / リポソーム再構成 |
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| Outline of Final Research Achievements |
The endoplasmic reticulum (ER) has distinct morphological domains, such as tubules and sheets. Although fatty acid metabolism is the one of the functions of the ER, its role in ER morphogenesis is unclear. In this study, we found that TER, an ER membrane enzyme catalyzing fatty acid elongation, directly bound to the ER Ca2+ pump SERCA2b. We then showed that TER limits the ER Ca2+ content by inhibiting SERCA2b activity. We further demonstrated that TER sustains cytosolic Ca2+ signaling. Given that Ca2+ regulates ER tubule morphology, these results suggest a possibility that TER regulates the ER tubule morphology by controlling cellular Ca2+ homeostasis.
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| Academic Significance and Societal Importance of the Research Achievements |
脂肪酸代謝酵素の個体レベルでの機能はノックアウト動物などを用いて解明が進んでいるが、分子レベルでの機能については不明な点が多い。本研究はTERがSERCA2bを介してCa2+動態を制御することを示すものであり、分子レベルで脂肪酸代謝酵素の機能を解明したという点で学術的な意義は大きいと考えている。また、SERCA2bの機能不全は表皮角化異常症 （ダリエ病） を引き起こす。本研究の結果はTERがSERCA2b活性を抑制することでダリエ病の病態形成に関わる可能性を示しており、社会的な意義も大きいと考えている。
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