Intracellular glucose 1-phosphate and glucose 6-phosphate levels modulate Ca2+ homeostasis in Saccharomyces cerevisiae.
The enzyme phosphoglucomutase plays a key role in cellular metabolism by virtue of its ability to interconvert Glc-1-P and Glc-6-P. It was recently shown that a yeast strain lacking the major isoform of phosphoglucomutase (pgm2Delta) accumulates a high level of Glc-1-P and exhibits several phenotypes related to altered Ca(2+) homeostasis when d-galactose is utilized as the carbon source (Fu, L., Miseta, A., Hunton, D., Marchase, R. B., and Bedwell, D. M. (2000) J. Biol. Chem. 275, 5431-5440). These phenotypes include increased Ca(2+) uptake and accumulation and sensitivity to high environmental Ca(2+) levels. In the present study, we overproduced the enzyme UDP-Glc pyrophosphorylase to test whether the overproduction of a downstream metabolite produced from Glc-1-P can also mediate changes in Ca(2+) homeostasis. We found that overproduction of UDP-Glc did not cause any alterations in Ca(2+) uptake or accumulation. We also examined whether Glc-6-P can influence cellular Ca(2+) homeostasis. A yeast strain lacking the beta-subunit of phosphofructokinase (pfk2Delta) accumulates a high level of Glc-6-P (Huang, D., Wilson, W. A., and Roach, P. J. (1997) J. Biol. Chem. 272, 22495-22501). We found that this increase in Glc-6-P led to a 1.5-2-fold increase in total cellular Ca(2+). We also found that the pgm2Delta/pfk2Delta strain, which accumulated high levels of both Glc-6-P and Glc-1-P, no longer exhibited the Ca(2+)-related phenotypes associated with high Glc-1-P levels in the pgm2Delta mutant. These results provide strong evidence that cellular Ca(2+) homeostasis is coupled to the relative levels of Glc-6-P and Glc-1-P in yeast.
D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D003470:Culture Media; D017931:DNA Primers; D005690:Galactose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D005958:Glucosephosphates / Q000378:metabolism*; D006706:Homeostasis; D025481:Phosphofructokinase-2 / Q000378:metabolism; D010733:Phosphoglucomutase / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase / Q000378:metabolism
D003470:Culture Media; D017931:DNA Primers; D005958:Glucosephosphates; D019298:Glucose-6-Phosphate; C031590:glucose-1-phosphate; D025481:Phosphofructokinase-2; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase; D010733:Phosphoglucomutase; D002118:Calcium; D005690:Galactose