Cdc14 phosphatase downmodulates ESCRT-0 complex formation on vacuolar membranes and microautophagy after TORC1 inactivation

Biochem Biophys Res Commun. 2021 Jul 5:561:158-164. doi: 10.1016/j.bbrc.2021.05.021. Epub 2021 May 21.

Abstract

Remodeling of vacuolar membranes mediated by endosomal sorting complex required for transport (ESCRT) is critical for microautophagy induction in budding yeast. Nutrient depletion and inactivation of target of rapamycin complex 1 (TORC1) protein kinase elicit recruitment of the ESCRT-0 complex (Vps27-Hse1) onto vacuolar membranes and ESCRT-mediated microautophagy induction. Mitotic protein phosphatase Cdc14 antagonizes TORC1-mediated phosphorylation in macroautophagy induction after nutrient starvation and TORC1 inactivation. Here, we report that Cdc14 downregulates microautophagy induction after TORC1 inactivation. Cdc14 dysfunction stimulated the vacuolar membrane recruitment of Hse1, but not Vps27, after TORC1 inactivation, promoting ESCRT-0 complex formation. Conversely, overexpression of CDC14 compromises Hse1 recruitment on vacuolar membranes and microautophagy induction after TORC1 inactivation. Thus, Cdc14 phosphatase regulates the fluxes of two types of autophagy in the opposite directions, namely, it elicits macroautophagy and attenuates microautophagy.

Keywords: Cdc14; ESCRT; Hse1; Microautophagy; TORC1; Vps27.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Intracellular Membranes / metabolism*
  • Intracellular Membranes / pathology
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Microautophagy
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Vacuoles / metabolism*
  • Vacuoles / pathology

Substances

  • CDC14 protein, S cerevisiae
  • Cell Cycle Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Hse1 protein, S cerevisiae
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • VPS27 protein, S cerevisiae
  • Mechanistic Target of Rapamycin Complex 1
  • Phosphoric Monoester Hydrolases
  • Protein Tyrosine Phosphatases