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A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits
Molecular Cell ( IF 14.5 ) Pub Date : 2020-11-17 , DOI: 10.1016/j.molcel.2020.10.030
Florian Wilfling 1 , Chia-Wei Lee 2 , Philipp S Erdmann 3 , Yumei Zheng 4 , Dawafuti Sherpa 5 , Stefan Jentsch 6 , Boris Pfander 7 , Brenda A Schulman 8 , Wolfgang Baumeister 3
Affiliation  

Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargo to the membrane-bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we report a selective autophagy pathway for protein condensates formed by endocytic proteins in yeast. In this pathway, the endocytic protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis and does not involve other known selective autophagy receptors but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates, at the plasma membrane and in autophagic bodies, shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy route. Our data suggest a model for autophagic degradation of macromolecular protein complexes by the action of intrinsic autophagy receptors.



中文翻译:


相分离内吞蛋白沉积的选择性自噬途径



自噬消除了自噬受体选择的细胞质内容物,自噬受体将货物与膜结合的自噬体泛素样蛋白 Atg8/LC3 连接起来。在这里,我们报告了酵母内吞蛋白形成的蛋白质缩合物的选择性自噬途径。在此通路中,内吞蛋白 Ede1 作为选择性自噬受体发挥作用。 Ede1 内的不同结构域结合 Atg8 并介导相分离成冷凝物。这两种特性对于内吞蛋白的 Ede1 依赖性自噬途径都是必需的,该途径与常规内吞作用不同,不涉及其他已知的选择性自噬受体,但需要核心自噬机制。对质膜和自噬体中含有 Ede1 的冷凝物进行冷冻电子断层扫描,显示在 Ede1 介导的选择性自噬途径的开始和结束处存在相分离的隔室。我们的数据提出了通过内在自噬受体的作用进行大分子蛋白质复合物自噬降解的模型。

更新日期:2020-12-03
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