Development of novel methods for allosteric activation of receptor subtypes on cell surface
Project/Area Number |
16H03290
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Chemical biology
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Research Institution | Kyoto University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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Keywords | グルタミン酸受容体 / ケミカルバイオロジー / アロステリック活性化 / サブタイプ / 細胞膜受容体 |
Outline of Final Research Achievements |
Development of new techniques for artificial regulation of specific cells in our body is one of essential technologies in life science researches. We have recently reported a new method for artifical activation of ion-channel-type glutamate receptors using coordination chemistry in live cells. In this method, two histidine mutations were introduced near the ligand-binding domain. Addition of Pd(bpy) complex, which coordinates to the histidine residues in a bidentate fashion, lead to stabilize the active conformation of the receptors for allosteric activation. Here, we successfully expanded our method for artificial regulation of G-protein coupled receptors (GPCRs). This means that our method is useful for artificial regulation of many kinds of receptors in live cells.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、我々の開発した受容体の人為的な活性化法が、イオンチャネル型受容体だけでなくGタンパク質共役型受容体も含めた幅広いタンパク質に対して拡張できる可能性を示した。また、この手法が神経細胞においても適用できることも確認した。この結果は、我々の方法論が、脳などの複雑な生体組織において狙った細胞の標的受容体を人為的に活性制御してその機能解明を行えるという、新たな方法論になり得ることを示唆する。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Chemical labelling for visualizing native AMPA receptors in live neurons.2017
Author(s)
Wakayama, S., Kiyonaka, S., Arai, I., Kakegawa, W., Matsuda, S., Ibata, K., Nemoto, Y.L., Kusumi, A., Yuzaki, M., Hamachi, I.
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Journal Title
Nature Communications
Volume: 8
Issue: 1
Pages: 14850-14850
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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