Yeast Calcium Homeostasis
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.
Genetically, biochemically, and also mathematically we are exploring calcium homeostasis and the ways yeast cell respond to extracellular and intracellular ion changes. Recently, Augustus Parker and David Mintz published their undergraduate thesis work from Barrett, the Honors College, analyzing intracellular calcium responses to both increases and decreases in extracellular calcium.
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.
Recently we discovered that a negative regulator of Channel X, Rch1p, is regulated by Cmk2p. When Cmk2p is activated, it putatively phosphorylates Rch1p, to move to the plasma membrane to inhibit Channel X.