Molecular Cell Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
Autophagy. 2021 Oct;17(10):3264-3265. doi: 10.1080/15548627.2021.1957567. Epub 2021 Aug 2.
Selective disposal of a wide range of cellular entities by macroautophagy/autophagy is achieved through a special class of proteins called autophagy receptors, which link corresponding cargo to the membrane-bound autophagosomal protein Atg8/LC3. In pursuit of novel autophagy receptors and their cargo, we uncovered a previously undescribed autophagy pathway for removal of aberrant clathrin-mediated endocytosis (CME) protein condensates in . Of these CME proteins, Ede1 functions as an autophagy receptor, harboring distinct Atg8-binding domains and driving phase separation into condensates. The aberrant CME condensates at the plasma membrane (PM) exhibit a drop-like structure surrounded by a fenestrated ER, which are engulfed in pieces in an Ede1-dependent manner by autophagy. Thus, our work suggests that aberrant CME is a target for autophagic degradation, with the scaffold protein Ede1 serving as a built-in autophagy receptor that monitors the assembly status of the CME machinery.
通过一类被称为自噬受体的特殊蛋白,细胞可以选择性地处理多种细胞实体,并将其与膜结合的自噬体蛋白 Atg8/LC3 连接起来。为了寻找新的自噬受体及其货物,我们在 中发现了一种以前未被描述的自噬途径,用于去除异常网格蛋白介导的内吞(CME)蛋白凝聚物。在这些 CME 蛋白中,Ede1 作为自噬受体发挥作用,具有独特的 Atg8 结合结构域,并驱动相分离成凝聚物。质膜(PM)上的异常 CME 凝聚物表现为一种滴状结构,周围是有窗孔的内质网,这些凝聚物以 Ede1 依赖的方式被自噬体以碎片的形式吞噬。因此,我们的工作表明,异常的 CME 是自噬降解的靶标,支架蛋白 Ede1 作为一种内置的自噬受体,监测 CME 机制的组装状态。