The glucose signal and metabolic p[H + ]lux

Eukaryotes harbour multiple signalling pathways to detect and respond to changes in glucose availability. Some of these pathways use plasma membrane receptors that sense extracellular glucose. Others are responsive to glycolytic flux and are activated by an elusive internal glucose signal. Many have proposed that a glycolytic intermediate serves dual functions as a metabolite and as a glucose signal. This issue of The EMBO Journal presents a study from [Dechant et al (2010)][1], which proposes that the glucose signal is elevated intracellular pH. An important player in the pH signalling pathway is the vacuolar ATPase, which reversibly assembles in response to elevated pH and activates the protein kinase A (PKA) pathway. This model is attractive in its simplicity. Could the elusive glucose signal be as simple as the concentration of protons? [1]: #ref-1