Genome-wide screen-based identification of non-selective hypertonicity-induced cation channel
| Project/Area Number |
17K15086
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Watanabe Kengo 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (20781727)
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| Research Collaborator |
MORISHITA Kazuhiro
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 高浸透圧ストレス / HICC / ゲノムワイドsiRNAスクリーニング / ASK3 / ストレス / シグナル伝達 |
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| Outline of Final Research Achievements |
Similar to slugs poured salt on, cells shrink when the concentration of extracellular solution becomes higher than that of intracellular solution, which is called as hyperosmotic stress. If this goes on, cells die; therefore, cells recover their volume to survive. To achieve cell volume recovery, cells firstly have to recognize the state under hyperosmotic stress. It is said that the protein passing ions, called HICC, is the cellular sensor for hyperosmotic stress; however, the molecular identity of HICC remains unclear. In this study, the scientist investigated about 20,000 proteins coded on the human genome one by one to identify the components of HICC. Although he could not surely identify it during this period, he successfully obtained the candidate protein and important knowledge establishing a foothold to further researches.
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| Academic Significance and Societal Importance of the Research Achievements |
液体と接している細胞は常に浸透圧ストレスに晒されるリスクがあり，浸透圧ストレスに適切に応答する仕組みは細胞が生存する上で必須の基本的なシステムの１つである．さらに細胞はこのシステムを浸透圧ストレスに対抗する時だけでなく，分裂や移動する時など体積を変化させる細胞機能時にも利用すると言われている．つまり，このシステムの異常が高血圧やがん，炎症などの疾患に関わっている可能性がある．本研究はシステムを始動させるセンサー部分に着目したものであり，本成果を足掛かりにシステムの全貌解明に向けてさらに研究を発展させることで，様々な疾患に対する創薬基盤・治療戦略の開発に資することが期待される．
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Cryo-EM structures of the human volume-regulated anion channel LRRC82018
Author(s)
Kasuya G, Nakane T, Yokoyama T, Jia Y, Inoue M, Watanabe K, Nakamura R, Nishizawa T, Kusakizako T, Tsutsumi A, Yanagisawa H, Dohmae N, Hattori M, Ichijo H, Yan Z, Kikkawa M, Shirouzu M, Ishitani R, Nureki O
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Journal Title
Nat Struct Mol Biol.
Volume: 25
Issue: 9
Pages: 797-804
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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