Comparative analysis of the single-molecule diffusion-function relationships of GPCR
Project/Area Number |
16K18533
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Biophysics
|
Research Institution | Institute of Physical and Chemical Research |
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)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
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 / 拡散・機能相関 / 1分子薬理学 / 全反射蛍光顕微鏡 / 拡散動態 / シグナル伝達 / 拡散係数 / 生物物理学 / 薬理学 / 生化学 |
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.
|
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。
|
Report
(4 results)
Research Products
(28 results)
-
-
-
[Journal Article] Pinopsin evolved as the ancestral dim-light visual opsin in vertebrates2018
Author(s)
Keita Sato, Takahiro Yamashita, Keiichi Kojima, Kazumi Sakai, Yuki Matsutani, Masataka Yanagawa, Yumiko Yamano, Akimori Wada, Naoyuki Iwabe, Hideyo Ohuchi, Yoshinori Shichida
-
Journal Title
Communications Biology
Volume: 1
Issue: 1
Pages: 156-156
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Adaptation of cone pigments found in green rods for scotopic vision through a single amino acid mutation2017
Author(s)
Keiichi Kojima , Yuki Matsutani , Takahiro Yamashita , Masataka Yanagawa , Yasushi Imamoto , Yumiko Yamano , Akimori Wada , Osamu Hisatomi , Kanto Nishikawa , Keisuke Sakurai , Yoshinori Shichida
-
Journal Title
Proceedings of the National Academy of Sciences
Volume: 印刷中
Related Report
Peer Reviewed
-
-
-
-
-
-
-
[Presentation] Single-molecule pharmacology of a GPCR2017
Author(s)
Masataka Yanagawa, Michio Hiroshima, Yuichi Togashi, Takahiro Yamashita, Yoshinori Shichida, Masahiro Ueda, Masayuki Murata, Yasushi Sako
Organizer
University of Strasbourg-RIKEN Workshop on Membrane Lipidology
Place of Presentation
Region Grand Est, France
Year and Date
2017-03-09
Related Report
Int'l Joint Research
-
-
-
[Presentation] Evolutionary acquisition of low thermal noise of cone pigments for scotopic vision2017
Author(s)
小島 慧一, 松谷 優樹, 柳川 正隆, 山下 高廣, 今元 泰, 久冨 修, 山野 由美子, 和田 昭盛, 七田 芳則
Organizer
日本生物物理学会第55回年会, 熊本, 2017
Related Report
-
[Presentation] Comparison of thermal activation rates between vertebrate visual pigments and pinopsin2017
Author(s)
山下 高廣, 佐藤 恵太, 小島 慧一, 酒井 佳寿美, 松谷 優樹, 柳川 正隆, 山野 由美子, 和田 昭盛, 岩部 直之, 大内 淑代, 七田 芳則
Organizer
日本生物物理学会第55回年会, 熊本, 2017
Related Report
-
-
-
-
-
-
-
-
-
-