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Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1613-1620. doi: 10.1073/pnas.1817078116. Epub 2019 Jan 17.

PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex.

Author information

1
Department of Biology, Brandeis University, Waltham, MA 02454.
2
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454.
3
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109.
4
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
5
Department of Biology, Brandeis University, Waltham, MA 02454; haber@brandeis.edu.

Abstract

Macroautophagy is orchestrated by the Atg1-Atg13 complex in budding yeast. Under nutrient-rich conditions, Atg13 is maintained in a hyperphosphorylated state by the TORC1 kinase. After nutrient starvation, Atg13 is dephosphorylated, triggering Atg1 kinase activity and macroautophagy induction. The phosphatases that dephosphorylate Atg13 remain uncharacterized. Here, we show that two redundant PP2C phosphatases, Ptc2 and Ptc3, regulate macroautophagy by dephosphorylating Atg13 and Atg1. In the absence of these phosphatases, starvation-induced macroautophagy and the cytoplasm-to-vacuole targeting pathway are inhibited, and the recruitment of the essential autophagy machinery to the phagophore assembly site is impaired. Expressing a genomic ATG13 -8SA allele lacking key TORC1 phosphorylation sites partially bypasses the macroautophagy defect in ptc2Δ ptc3Δ strains. Moreover, Ptc2 and Ptc3 interact with the Atg1-Atg13 complex. Taken together, these results suggest that PP2C-type phosphatases promote macroautophagy by regulating the Atg1 complex.

KEYWORDS:

ATG13; PP2C phosphatases; Saccharomyces cerevisiae; autophagy

PMID:
30655342
PMCID:
PMC6358665
[Available on 2019-07-29]
DOI:
10.1073/pnas.1817078116
[Indexed for MEDLINE]

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