Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), Carrer del doctor Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Carrer del doctor Aiguader 88, 08003 Barcelona, Spain.
Electron Microscopy Core Facility, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Science. 2014 Nov 7;346(6210):751-5. doi: 10.1126/science.1255638. Epub 2014 Sep 18.
Misfolded proteins in the endoplasmic reticulum (ER) are eliminated by a quality control system called ER-associated protein degradation (ERAD). However, it is unknown how misfolded proteins in the inner nuclear membrane (INM), a specialized ER subdomain, are degraded. We used a quantitative proteomics approach to reveal an ERAD branch required for INM protein quality control in yeast. This branch involved the integral membrane proteins Asi1, Asi2, and Asi3, which assembled into an Asi complex. Besides INM misfolded proteins, the Asi complex promoted the degradation of functional regulators of sterol biosynthesis. Asi-mediated ERAD was required for ER homeostasis, which suggests that spatial segregation of protein quality control systems contributes to ER function.
内质网（ER）中的错误折叠蛋白通过一种称为 ER 相关蛋白降解（ERAD）的质量控制系统被清除。然而，内质网中内核膜（INM）内的错误折叠蛋白是如何被降解的，目前还不清楚。我们使用一种定量蛋白质组学方法来揭示酵母中用于 INM 蛋白质质量控制的 ERAD 分支。这个分支涉及到整合膜蛋白 Asi1、Asi2 和 Asi3，它们组装成 Asi 复合物。除了 INM 错误折叠的蛋白质，Asi 复合物还促进固醇生物合成的功能调节剂的降解。Asi 介导的 ERAD 对于 ER 稳态是必需的，这表明蛋白质质量控制系统的空间隔离有助于 ER 功能。
