| 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 |
|---|
| 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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