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.
Department of Microbiology and Molecular Medicine, University of Geneva Medical School, 1211 Geneva 4, Switzerland.
Frédérique
F
Dubouloz
Olivier
O
Deloche
Valeria
V
Wanke
Elisabetta
E
Cameroni
Claudio
C
De Virgilio
D000935:Antifungal Agents / Q000494:pharmacology; D001343:Autophagy; D002462:Cell Membrane / Q000187:drug effects; D005456:Fluorescent Dyes; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005973:Glutamine / Q000378:metabolism; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins; D011233:Precipitin Tests; D040081:Protein Array Analysis; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D014617:Vacuoles / Q000187:drug effects
D000935:Antifungal Agents; C092350:FM 4-64; D005456:Fluorescent Dyes; D005656:Fungal Proteins; C121263:GTR2 protein, S cerevisiae; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D029701:Saccharomyces cerevisiae Proteins; D005973:Glutamine; D019204:GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins; D020123:Sirolimus