Investigation of the effect of calcium signaling pathway on the cell cycle regulation and transcription of genes that involves in glucose metabolism

Calcium is an important biometal ion and acts as an activator of signaling pathways in controlling many metabolic events in cells. The effects of calcium signaling are exerted through the calcium/calmodulin pathway. Crz1 is the transcription activator that activates the transcription of numerous genes in response to calcium signaling in yeast. Glucose is an important carbon and energy source for yeast and transported into yeast cells by hexose transporters (Hxts) via facilitated diffusion mechanisms. Transcription of HXT genes is regulated by different metabolic signals including external glucose concentration. Glucose can be metabolized in the glycolytic pathway. Besides, it can be converted in to reserve carbohydrates trehalose and glycogen in yeast. In this study, we have investigated the effects of calcium signaling on the expression of HXT2, HXT4, and TPS1 genes that are required for glucose transport and trehalose biosynthesis, respectively. Our results indicated that calcium signaling activates transcription of HXT2, HXT4, and TPS1 genes under glucose repressed conditions. Interestingly, calcium did not have any effects on the transcription of these genes under glucose derepressed growth conditions. Also, it appears that protein kinases Hog1p and Snf1p involves partially in the calcium-dependent activation of basal transcription in HXT2, HXT4, and TPS1 genes. We have also investigated the effects of calcium signaling on the growth rate and cell cycle regulation in yeast. Our results show that calcium acts on the cell cycle via Snf1 kinase and affects the G1 to S transition stage since calcium stops cell cycle in G1 stage in snf1 mutant yeasts. Calcium also interferes with the growth rate in yeast. Furthermore, our results indicated that calcium ions activate the glycogen storage in hog1 kinase-deficient yeasts. In silico analyses of the promoter regions of HXT2, HXT4 and TPS1 genes indicated that transcription of these genes is activated by multiple regulatory factors whose activities depend on calcium signaling.