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Vps13 is required for the packaging of the ER into autophagosomes during ER-phagy

Shuliang Chen, Muriel Mari, Smriti Parashar, Dongmei Liu, Yixian Cui, Fulvio Reggiori, Peter Novick, Susan Ferro‐Novick

2020Proceedings of the National Academy of Sciences61 citationsDOIOpen Access PDF

Abstract

, humans have four vacuolar protein-sorting (VPS) protein 13 isoforms. Mutations in all four human isoforms have been linked to different neurological disorders, including Parkinson's disease. Our findings have shown that Vps13 acts after Atg40 engages the autophagy machinery. Vps13 resides at contact sites between the ER and several organelles, including late endosomes. In the absence of Vps13, the cortical ER marker Rtn1 accumulated at late endosomes, and a dramatic decrease in ER packaging into autophagosomes was observed. Together, these studies suggest a role for Vps13 in the sequestration of the ER into autophagosomes at late endosomes. These observations may have important implications for understanding Parkinson's and other neurological diseases.

Topics & Concepts

Endoplasmic reticulumEndosomeCell biologyAutophagyMitophagyOrganelleAutophagosomeSaccharomyces cerevisiaeBiologyTransport proteinMutantFunction (biology)YeastChemistryGeneGeneticsIntracellularApoptosisAutophagy in Disease and TherapyEndoplasmic Reticulum Stress and DiseaseCellular transport and secretion