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


Dechant, Reinhard; Binda, Matteo; Lee, Sung Sik; Pelet, Serge; Winderickx, Joris; Peter, Matthias (2010). Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V‐ATPase. EMBO Journal Online, 29(15):2515-2526.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:Special Collections > SystemsX.ch
Special Collections > SystemsX.ch > Research, Technology and Development Projects > YeastX
Special Collections > SystemsX.ch > Research, Technology and Development Projects
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2010
Deposited On:03 Jul 2013 07:33
Last Modified:07 Aug 2017 11:21
Publisher:Nature Publishing Group
ISSN:0261-4189
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/emboj.2010.138
PubMed ID:20581803

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