| Project/Area Number |
24657094
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Gタンパク質 / シグナル伝達 / 分解経路 / リソソーム / FRET / G蛋白質 / 後期エンドソーム / Rab7 / Rab5 |
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| Outline of Final Research Achievements |
Rab7 is known to be a key molecule which regulates dynamics of lysosomes, in which a variety of biomolecules and damaged organelles are destructed. In this study, I have developed a FRET sensor, Raichu-Rab7, which can visualize the spatiotemporal change of Rab7 activity in living cells. Raichu-Rabs7 has shown the existence of a significant variation in Rab7 activity of individual endosomes in steady-state COS-7 cells. Next, I investigated the mechanism regulating Rab7 activity during the process from late endosomes to lysosomes in steady-state cells and macropinocytosis in EGF-stimulated COS-7 cells. Based on these studies, I have concluded that Rab7 on late endosomes is activated by Mon1/Ccz1 complex and plays an essential role in the fusion between late endosome and lysosome; on the contrary, Rab7 activation on lysosomes is independent of Mon1/Ccz1 and active Rab7 on lysosomes is implicated in the perinuclear accumulation of lysosomes.
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