Molecular mechanism of trafficking regulation of G protein-coupled receptor
| Project/Area Number |
25460326
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Shiga University of Medical Science (2014-2015)
Hokkaido University (2013) |
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Principal Investigator |
Terada Koji 滋賀医科大学, 医学部, 准教授 (70342722)
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| Co-Investigator(Renkei-kenkyūsha) |
MIWA Soichi 北海道大学, 大学院医学研究科, 教授 (40157706)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | エンドセリン / ユビキチン / エンドサイトーシス / リサイクリング / エンドセリン受容体 / ユビキチン化 / Gタンパク質共役受容体 |
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| Outline of Final Research Achievements |
Two types of G protein-coupled receptors for endothelin-1 (ET-1), ET type A receptor (ETAR) and ETBR, resemble each other, but upon ET-1 stimulation, they follow different intracellular trafficking pathways. In this study, we showed that ETBR but not ETAR was ubiquitinated upon ET-1 stimulation, and that ETBR was internalized and degraded in lysosome more rapidly than ETAR. The mutant ETBR (designated “5KR mutant”) in which 5 lysine residues in C-tail were substituted to arginine was not ubiquitinated, and its rates of internalization and degradation after ET-1 stimulation became slower. Confocal microscopic study showed that following ET-1 stimulation, ETAR and 5KR mutant of ETBR were co-localized mainly with Rab11, a marker of recycling endosome, whereas ETBR was with Rab7, a marker of late endosome/lysosome. These results demonstrate that agonist-induced ubiquitination in C-tail of ETBR switches intracellular trafficking from recycling to plasma membrane to targeting to lysosome.
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Agonist-promoted ubiquitination differentially regulates receptor trafficking of endothelin type A and type B receptors.2014
Author(s)
Terada K., Horinouchi T., Fujioka Y., Higashi T., Nepal P., Horiguchi M., Sarita K., Hatate C., Hoshi A., Harada T., Mai Y., Ohba Y. and Miwa S.
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Journal Title
J. Biol. Chem.
Volume: 289
Pages: 35283-35295
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A simple and rapid method for standard preparation of gas phase extract of cigarette smoke.2014
Author(s)
Higashi T., Mai Y., Noya Y., Horinouchi T., Terada K., Hoshi A., Nepal P., Harada T., Horiguchi M., Hatate C., Kuge Y. and Miwa S.
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Journal Title
PLos ONE
Volume: 9
Pages: -
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements.2014
Author(s)
Mizuhashi K., Kanamoto T., Moriishi T., Muranishi Y., Miyazaki T., Terada K., Omori Y., Ito M., Komori T. and Furukawa T.
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Journal Title
Hum. Mol. Genet.
Volume: 23
Pages: 2953-2967
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of stable cytotoxic factors in the gas phase extract of cigarette smoke and pharmacological characterization of their cytotoxicity2013
Author(s)
Noya Y., Seki K., Asano H., Mai Y., Horinouchi T., Higashi T., Terada K., Hatate C., Hoshi A., Nepal P., Horiguchi M., Kuge Y. and Miwa, S.
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Journal Title
Toxicology
Volume: 314
Pages: 1-10
DOI
Related Report
Peer Reviewed
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