2020 Fiscal Year Final Research Report
Molecular mechanism underlying induction of spontaneous excitation by GPCR and its physiological significance
| Project/Area Number |
19K22443
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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 44:Biology at cellular to organismal levels, and related fields
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| Research Institution | Kyushu University (2020)
Center for Novel Science Initatives, National Institutes of Natural Sciences (2019) |
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Principal Investigator |
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Keywords | GPCR / 自発活性 / 炎症 |
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| Outline of Final Research Achievements |
G protein-coupled receptors (GPCRs) are membrane proteins that convert extracellular physicochemical stimuli into intracellular signal transduction. Every GPCR uses their characteristic chemical substance as a selective ligand, and the signal is turned on when the ligand binds to the GPCR. We newly found that out of 250 types of GPCRs, at least 7 types of GPCRs (GPR-Xs) have a ligand-independent activation property (i.e., spontaneous activity). We revealed using genetically modified mice that P2Y6R, one of the GPR-Xs, regulates cardiac stress resistance, and suggested a potentiality of these GPCRs as new therapeutic targets.
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| Free Research Field |
薬理学、生理学
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| Academic Significance and Societal Importance of the Research Achievements |
Gタンパク質共役型受容体（GPCR）は、細胞外のホルモン情報を細胞内に伝達する重要なセンサーであり、創薬標的としても非常によく注目される膜タンパク質である。教科書的には、GPCRはホルモンや神経伝達物質などのリガンドによってのみ活性化されると信じられてきたが、我々はGPCRが存在する場の環境変化によって自発的に活性化することを明らかにした。この知見は、リガンド－GPCR結合様式でのみ考えられてきたGPCR創薬研究を見直すきっかけとなり、新たな疾患治療のストラテジー構築につながる可能性が期待できる。
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