2018 Fiscal Year Final Research Report
Comparative analysis of the single-molecule diffusion-function relationships of GPCR
| Project/Area Number |
16K18533
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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 |
Biophysics
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Yanagawa Masataka 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (70609792)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | GPCR / 1分子イメージング / 拡散機能相関 / 代謝型グルタミン酸受容体 |
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| Outline of Final Research Achievements |
G protein-coupled receptors (GPCRs) are major drug targets. However, it is difficult to measure the effects of a drug by monitoring each receptor molecule in a living cell. Here, we show that single-molecule imaging analysis provides an alternative method for assessing ligand effects on GPCRs. First, we demonstrate that the diffusion coefficient of metabotropic glutamate receptor 3 is tightly coupled with its functional states including G protein binding and clathrin-dependent endocytosis. Then, we confirmed the generality of diffusion-function relationship to many GPCRs regardless of the coupling specificity to G proteins. The present study provide a novel applicability of the single-molecule imaging in pharmacology and drug screening.
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| Free Research Field |
生物物理学・薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
GPCRは創薬の主要な標的分子となっている。本研究で明らかにした「受容体の拡散と機能の関係」は多くのGPCRに共通しているため、拡散を定量することで下流の細胞応答の異なる様々なGPCRに対する薬効を共通の指標で評価できるようになると期待される。
したがって、本研究成果は、1分子レベルで薬の作用機序を理解する1分子薬理学の発展や、1分子イメージングを用いたGPCR標的化合物の薬効評価という新たなドラッグスクリーニング手法の開発に貢献すると期待できる。
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