title: Cytosolic pH regulates cell growth through distinct GTPases, Arf1 and Gtr1, to promote Ras/PKA and TORC1 activity.
abstract: Regulation of cell growth by nutrients is governed by highly conserved signaling pathways, yet mechanisms of nutrient sensing are still poorly understood. In yeast, glucose activates both the Ras/PKA pathway and TORC1, which coordinately regulate growth through enhancing translation and ribosome biogenesis and suppressing autophagy. Here, we show that cytosolic pH acts as a cellular signal to activate Ras and TORC1 in response to glucose availability. We demonstrate that cytosolic pH is sensitive to the quality and quantity of the available carbon source (C-source). Interestingly, Ras/PKA and TORC1 are both activated through the vacuolar ATPase (V-ATPase), which was previously identified as a sensor for cytosolic pH in vivo. V-ATPase interacts with two distinct GTPases, Arf1 and Gtr1, which are required for Ras and TORC1 activation, respectively. Together, these data provide a molecular mechanism for how cytosolic pH links C-source availability to the activity of signaling networks promoting cell growth.
authors.affiliation: Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland; Competence Center for Systems Physiology and Metabolic Diseases, 8093 Zurich, Switzerland. Electronic address: reinhard.dechant@bc.biol.ethz.ch.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dechant
authors.affiliation: Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland; Life Science Zurich, PhD Program Systems Biology of Complex Diseases, 8093 Zurich, Switzerland.
authors.forename: Shady
authors.initials: S
authors.lastname: Saad
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Ibáñez
authors.affiliation: Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland; Competence Center for Systems Physiology and Metabolic Diseases, 8093 Zurich, Switzerland. Electronic address: matthias.peter@bc.biol.ethz.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism* / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
chemical_list: C121262:Gtr1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D025262:Vacuolar Proton-Translocating ATPases; D020823:ADP-Ribosylation Factor 1; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins; D005947:Glucose