The TOR and EGO protein complexes orchestrate microautophagy in yeast.
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.
Mesh Terms:
Antifungal Agents, Autophagy, Cell Membrane, Fluorescent Dyes, Fungal Proteins, GTP-Binding Proteins, Gene Deletion, Gene Expression Profiling, Glutamine, Immunoblotting, Microscopy, Fluorescence, Models, Biological, Monomeric GTP-Binding Proteins, Precipitin Tests, Protein Array Analysis, Pyridinium Compounds, Quaternary Ammonium Compounds, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sirolimus, Time Factors, Two-Hybrid System Techniques, Vacuoles
Antifungal Agents, Autophagy, Cell Membrane, Fluorescent Dyes, Fungal Proteins, GTP-Binding Proteins, Gene Deletion, Gene Expression Profiling, Glutamine, Immunoblotting, Microscopy, Fluorescence, Models, Biological, Monomeric GTP-Binding Proteins, Precipitin Tests, Protein Array Analysis, Pyridinium Compounds, Quaternary Ammonium Compounds, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sirolimus, Time Factors, Two-Hybrid System Techniques, Vacuoles
Mol. Cell
Date: Jul. 01, 2005
PubMed ID: 15989961
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