Yeast Calcium Homeostasis

Genetically, biochemically, and also mathematically we are exploring calcium homeostasis and the ways yeast cell respond to extracellular and intracellular ion changes.  Recently, Jennifer Kepler published her undergraduate thesis work from Barrett, the Honors College, demonstrating that there is a feedback mechanism to inhibit Yvc1p after extracellular calcium increases.  

We also have been exploring mathematically this calcium homeostasis, and this work includes modeling with and without key protein players.  

This is our control block diagram of calcium homeostasis.  We let m(t), z(t), h(t), x(t) denote the concentration of Ca2+-bound calmodulin, the concentration of activated calcineurin, total nuclear fraction of Crz1p, and cytosolic calcium ion concentration respectively. 

We and others have shown that in the presence of high extracellular calcium, the cellular rapid feedback response sequesters calcium into the vacuole via Vcx1p and Pmc1p and into the ER/Golgi apparatus via Pmr1p. Our current results show that calcium chloride treatment of the calmodulin kinase 1 double mutant eliminates the calcium leak seen in previous lab work. Cells with a deletion of cmk1 are leaking calcium through the vacuolar calcium exporter, Yvc1p; therefore during a slower feedback response in the cell’s return to homeostasis, calmodulin kinase 1 is a regulator of Yvc1p.