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A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits.


ABSTRACT: 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.

SUBMITTER: Wilfling F 

PROVIDER: S-EPMC7721475 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits.

Wilfling Florian F   Lee Chia-Wei CW   Erdmann Philipp S PS   Zheng Yumei Y   Sherpa Dawafuti D   Jentsch Stefan S   Pfander Boris B   Schulman Brenda A BA   Baumeister Wolfgang W  

Molecular cell 20201117 5


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 aut  ...[more]

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