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

Proceedings of the National Academy of Sciences of the United States of America
Shuliang ChenSusan Ferro-Novick

Abstract

Endoplasmic reticulum (ER) macroautophagy (hereafter called ER-phagy) uses autophagy receptors to selectively degrade ER domains in response to starvation or the accumulation of aggregation-prone proteins. Autophagy receptors package the ER into autophagosomes by binding to the ubiquitin-like yeast protein Atg8 (LC3 in mammals), which is needed for autophagosome formation. In budding yeast, cortical and cytoplasmic ER-phagy requires the autophagy receptor Atg40. While different ER autophagy receptors have been identified, little is known about other components of the ER-phagy machinery. In an effort to identify these components, we screened the genome-wide library of viable yeast deletion mutants for defects in the degradation of cortical ER following treatment with rapamycin, a drug that mimics starvation. Among the mutants we identified was vps13Δ. While yeast has one gene that encodes the phospholipid transporter VPS13, 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 bet...Continue Reading

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Citations

Nov 20, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Mohamed A EldeebDoaa S Salah El-Din
Jan 30, 2021·Trends in Biochemical Sciences·Susan Ferro-NovickJeffrey L Brodsky
Mar 7, 2021·International Journal of Molecular Sciences·Piotr SoczewkaJoanna Kaminska
Apr 4, 2021·International Journal of Molecular Sciences·Samantha Katarzyna Dziurdzik, Elizabeth Conibear
Jul 3, 2021·International Journal of Molecular Sciences·Jae-Sook ParkAaron M Neiman
Jul 4, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Marianna LeonzinoPietro De Camilli
Oct 30, 2021·The Journal of Cell Biology·Sunandini ChandraC Patrick Lusk

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