Title
Cytosolic pH regulates cell growth through distinct gtpases, Arf1 and Gtr1, to promote ras/PKA and TORC1 activity
Date Issued
07 August 2014
Access level
open access
Resource Type
journal article
Author(s)
Dechant R.
Saad S.
Peter M.
Universidad pública en Zurich, Suiza
Publisher(s)
Cell Press
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. © 2014 Elsevier Inc.
Start page
409
End page
421
Volume
55
Issue
3
Language
English
OCDE Knowledge area
Bioquímica, Biología molecular Biología celular, Microbiología Oncología Biotecnología relacionada con la salud
Scopus EID
2-s2.0-84906101389
PubMed ID
Source
Molecular Cell
ISSN of the container
10972765
Sponsor(s)
Seventh Framework Programme - 268930 - FP7 We thank Robbie Loewith, Claudio De Virgilio, Enzo Martegani, and Monika Kijanska for antibodies and plasmids; Renato Zenobi, Claudine Kraft, Alicia Smith, Sung Sik Lee, and Serge Pelet for helpful discussions and critical reading of the manuscript; and Raymond Buser and Anet Allik for providing IgG-coupled magnetic beads. A.J.I. is supported through the Ambizione Program of the Swiss National Science Foundation (SNF; PZ00P3_142615) and gratefully acknowledges AB Sciex for granting access to the AB5800 instrument. Work in the Peter (M.P.) laboratory is supported by the European Research Council, the SNF, the Swiss Initiative in Systems Biology SystemsX (RTD projects YeastX and LiverX), and the ETH Zürich.
Sources of information: Directorio de Producción Científica Scopus