| Project/Area Number |
25292177
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Veterinary medical science
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| Research Institution | Hokkaido University |
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Principal Investigator |
INABA Mutsumi 北海道大学, (連合)獣医学研究科, 教授 (00183179)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Kota 北海道大学, 大学院獣医学研究科, 准教授 (50283974)
YAMAMORI Toru 北海道大学, 大学院獣医学研究科, 准教授 (00512675)
大塚 沙織 北海道大学, (連合)獣医学研究科, 助教 (10566152)
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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 |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | 小胞体関連分解 / 膜蛋白質 / 遺伝性疾患 / 小胞体品質管理 / プロテアソーム / 蛋白質分解 / Derlin / 小胞体シャペロン / ユビキチン / ERシャペロン |
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| Outline of Final Research Achievements |
The ER-associated degradation (ERAD) of R664X AE1 is characteristic because it occurs in the ER membrane in a Ub-independent manner. The roles of pseudo-rhomboid proteins, Derlin-1 and -2 in the ERAD of mutant membrane proteins were investigated in the cells expressing R664X, R845X, and ΔCD mutants. Derlins 1 and 2 and their chimeric proteins associated with R664X AE1 and reduction of Derlins caused significant decreases in the contents of R664X AE1.Although R664X or R845X and ΔCD showed remarkable difference in the intracellular distribution resembling their distinct retrotranslocation, breakdown of these mutants were reduced when the expression of Derlins was inhibited. These findings demonstrate that Derlins play key roles in the ERAD of membrane proteins despite of the difference in retrotranslocation from the ER of the substrates.
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