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研究揭示Atg9是膜形成的“种子”

时间:2020-09-05 13:10来源:葡京捕鱼赌场 作者:葡京娱乐 点击:
本期文章:《科学》:Volume 369 Issue 6508 奥地利维也纳大学Sascha Martens和Justyna Sawa-Makarska课题组合作取得最新进展。他们揭示了自噬体成核的重建将自噬相关的蛋白质9(Atg9)囊泡定义为

本期文章:《科学》:Volume 369 Issue 6508

奥地利维也纳大学Sascha Martens和Justyna Sawa-Makarska课题组合作取得最新进展。他们揭示了自噬体成核的重建将自噬相关的蛋白质9(Atg9)囊泡定义为膜形成的种子。该研究于2020年9月4日发表于《科学》。

他们使用酵母的重组成分重建了自噬体。他们发现Atg9蛋白脂质体首先募集了磷脂酰肌醇3-磷酸激酶复合物,然后募集了Atg21,Atg2-Atg18脂质转移复合物和E3样Atg12–Atg5-Atg16复合物,从而促进了Atg8脂质化。此外,他们发现Atg2可以为Atg8脂质化转移脂质。在选择性自噬中,这些反应可能会通过Atg19-Atg11-Atg9相互作用与货物偶联。因此,他们提出Atg9囊泡形成种子,该种子建立膜接触位点以启动脂质从隔室(例如内质网)的转移。

据介绍,自噬体可以从头合成,但是这种方式还未被完全了解。Atg9囊泡尤其没有研究透彻,这是自噬机器组装所必需的,但不提供大部分的自噬体膜。

附:英文原文

Title: Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation

Author: Justyna Sawa-Makarska, Verena Baumann, Nicolas Coudevylle, Sren von Bülow, Veronika Nogellova, Christine Abert, Martina Schuschnig, Martin Graef, Gerhard Hummer, Sascha Martens

Issue&Volume: 2020/09/04

Abstract: Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)–containing vesicles that are required for autophagy machinery assembly but do not supply the bulk of the autophagosomal membrane. In this study, we reconstituted autophagosome nucleation using recombinant components from yeast. We found that Atg9 proteoliposomes first recruited the phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, the Atg2-Atg18 lipid transfer complex, and the E3-like Atg12–Atg5-Atg16 complex, which promoted Atg8 lipidation. Furthermore, we found that Atg2 could transfer lipids for Atg8 lipidation. In selective autophagy, these reactions could potentially be coupled to the cargo via the Atg19-Atg11-Atg9 interactions. We thus propose that Atg9 vesicles form seeds that establish membrane contact sites to initiate lipid transfer from compartments such as the endoplasmic reticulum.

DOI: 10.1126/science.aaz7714

Source: https://science.sciencemag.org/content/369/6508/eaaz7714

期刊信息

Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037

官方网址:https://www.sciencemag.org/

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