Roles of pseudo-rhomboid protein Derlins in the Ub-independent ER-associated degradation of membrane proteins

2015 Fiscal Year Final Research Report

• Project/Area Number: 25292177
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: INABA Mutsumi 北海道大学, (連合)獣医学研究科, 教授 (00183179)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 小胞体関連分解 / 膜蛋白質 / 遺伝性疾患 / 小胞体品質管理

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.

Free Research Field

分子医学