Study on the molecular mechanism underlying the posttranslational insertion of tail-anchored proteins into the endoplasmic reticulum membrane

2014 Fiscal Year Final Research Report

• Project/Area Number: 24570157
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kobe University
• Principal Investigator: YAMAMOTO YASUNORI 神戸大学, 医学(系)研究科(研究院), 講師 (30467659)
• Co-Investigator(Renkei-kenkyūsha): SAKISAKA Toshiaki 神戸大学, 大学院医学研究科, 教授 (80359843)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 小胞体 / 尾部アンカー型膜タンパク質 / テイルアンカ－型タンパク質 / 膜挿入装置 / CAML複合体 / 膜変形タンパク質

Outline of Final Research Achievements

Tail-anchored proteins (TA proteins) are localized at various endomembrane compartments and play essential roles in cellular homeostasis. TA proteins are posttranslationally inserted into the endoplasmmic reticulum (ER) membrane, followed by vesicular traffic to their final destinations. However, little is known about the molecular mechanism underlying the posttranslational membrane insertion.
In this study, we revealed that two ER membrane proteins, CAML and WRB, constituted the molecular machinery for the membrane insertion of TA proteins in mammalian cells. We identified the CAML-binding proteins responsible for regulating the membrane insertase activity of the CAML－WRB complex. We also identified a novel ER membrane-shaping protein and its binding protein responsible for regulating the membrane-shaping activity. Thus, this study uncovered the molecular identity of the membrane inseratse for TA proteins and helped us understand the mechanism of the membrane protein insertion.

Free Research Field

生化学