| Project/Area Number |
15K07939
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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 |
Biological pharmacy
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
GOTO NAOMI 岩手医科大学, 薬学部, 助教 (80403971)
SEKIYA MIZUKI 岩手医科大学, 薬学部, 助教 (70509033)
WADA GE-HONG (SUN GE-HONG) 同志社女子大学, 薬学部, 教授 (00314427)
WADA YOH 大阪大学, 産業科学研究所, 准教授 (50212329)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | プロトンポンプ / 酸性環境 / オルガネラ輸送 / 破骨細胞 / ATPase / 分泌リソソーム / Rab7 / Rab27 / V-ATPase / 骨吸収 / 液胞型プロトンポンプ / 小胞輸送 |
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| Outline of Final Research Achievements |
Osteoclast secretory lysosomes move toward the plasma membrane and release their enzymes required for bone resorption. We have shown that a3 isoform of proton-pumping V-ATPase has an essential role in outward trafficking of secretory lysosomes. The a3 is lysosome-specific isoform of the a subunit that forms the proton pathway in V-ATPase. Using a3-knockout mice, we found that a3 is indispensable for recruitment of Rab7, a small GTPase involved in lysosome trafficking. We also found that a3 specifically interacts with inactivated-form of Rab7. These results suggest that a3 recruits Rab7 to secretory lysosomes through their direct interaction. Secretory lysosomes are involved in various cell type-specific functions, such as secretion of pore-forming protein from cytotoxic T cells and metastasis of cancer cells. Thus, our findings will provide a new insight into these functions, and promote development of novel treatments for related diseases.
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