The TOR and EGO protein complexes orchestrate microautophagy in yeast

Mol Cell. 2005 Jul 1;19(1):15-26. doi: 10.1016/j.molcel.2005.05.020.

Abstract

The rapamycin-sensitive TOR signaling pathway in Saccharomyces cerevisiae positively controls cell growth in response to nutrient availability. Accordingly, TOR depletion or rapamycin treatment causes regulated entry of cells into a quiescent growth phase. Although this process has been elucidated in considerable detail, the transition from quiescence back to proliferation is poorly understood. Here, we describe the identification of a conserved member of the RagA subfamily of Ras-related GTPases, Gtr2, which acts in a vacuolar membrane-associated protein complex together with Ego1 and Ego3 to ensure proper exit from rapamycin-induced growth arrest. We demonstrate that the EGO complex, in conjunction with TOR, positively regulates microautophagy, thus counterbalancing the massive rapamycin-induced, macroautophagy-mediated membrane influx toward the vacuolar membrane. Moreover, large-scale genetic analyses of the EGO complex confirm the existence of a growth control mechanism originating at the vacuolar membrane and pinpoint the amino acid glutamine as a key metabolite in TOR signaling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology
  • Autophagy*
  • Cell Membrane / drug effects
  • Fluorescent Dyes
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Profiling
  • Glutamine / metabolism
  • Immunoblotting
  • Microscopy, Fluorescence
  • Models, Biological
  • Monomeric GTP-Binding Proteins
  • Precipitin Tests
  • Protein Array Analysis
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Sirolimus / pharmacology
  • Time Factors
  • Two-Hybrid System Techniques
  • Vacuoles / drug effects

Substances

  • Antifungal Agents
  • FM 4-64
  • Fluorescent Dyes
  • Fungal Proteins
  • GTR2 protein, S cerevisiae
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Saccharomyces cerevisiae Proteins
  • Glutamine
  • GTP-Binding Proteins
  • Monomeric GTP-Binding Proteins
  • Sirolimus