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Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V‐ATPase

Reinhard Dechant, Matteo Binda, Sung Sik Lee, Serge Pelet, Joris Winderickx, Matthias Peter

Author Affiliations

  1. Reinhard Dechant*,1,2,
  2. Matteo Binda3,,
  3. Sung Sik Lee1,2,
  4. Serge Pelet1,2,
  5. Joris Winderickx3 and
  6. Matthias Peter*,1,2
  1. 1 Institute of Biochemistry, ETH Zurich, Zurich, Switzerland
  2. 2 Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
  3. 3 Functional Biology, Katholieke Universiteit Leuven, Leuven‐Heverlee, Belgium
  1. *Corresponding authors. Institute of Biochemisty, ETH Zurich, Schafmattstr 19, Zuerich 8093, Switzerland. Tel.: +41 44 63 36 584; Fax: +41 44 633 12 28; E-mail: reinhard.dechant{at} or Tel.: +41 44 63 36 586; Fax: +41 44 633 12 28; E-mail: matthias.peter{at}
  • Present address: Department of Biology, University of Fribourg, Fribourg CH‐1700, Switzerland

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Glucose is the preferred carbon source for most cell types and a major determinant of cell growth. In yeast and certain mammalian cells, glucose activates the cAMP‐dependent protein kinase A (PKA), but the mechanisms of PKA activation remain unknown. Here, we identify cytosolic pH as a second messenger for glucose that mediates activation of the PKA pathway in yeast. We find that cytosolic pH is rapidly and reversibly regulated by glucose metabolism and identify the vacuolar ATPase (V‐ATPase), a proton pump required for the acidification of vacuoles, as a sensor of cytosolic pH. V‐ATPase assembly is regulated by cytosolic pH and is required for full activation of the PKA pathway in response to glucose, suggesting that it mediates, at least in part, the pH signal to PKA. Finally, V‐ATPase is also regulated by glucose in the Min6 β‐cell line and contributes to PKA activation and insulin secretion. Thus, these data suggest a novel and potentially conserved glucose‐sensing pathway and identify a mechanism how cytosolic pH can act as a signal to promote cell growth.

There is a Have you seen ...? (August 2010) associated with this Article.

  • Received January 28, 2010.
  • Accepted May 28, 2010.
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