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Mol Cell. 2014 Aug 7;55(3):409-21. doi: 10.1016/j.molcel.2014.06.002. Epub 2014 Jul 4.

Cytosolic pH regulates cell growth through distinct GTPases, Arf1 and Gtr1, to promote Ras/PKA and TORC1 activity.

Author information

1
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.
2
Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland; Life Science Zurich, PhD Program Systems Biology of Complex Diseases, 8093 Zurich, Switzerland.
3
Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
4
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.

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.

PMID:
25002144
DOI:
10.1016/j.molcel.2014.06.002
[Indexed for MEDLINE]
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