Abstract
We study, both experimentally and through mathematical modeling, the response of wild type and mutant yeast strains to systematic variations of extracellular calcium abundance. We extend a previously developed mathematical model (Cui and Kaandorp, Cell Calcium, 39, 337 (2006))[3], that explicitly considers the population and activity of proteins with key roles in calcium homeostasis. Modifications of the model can directly address the responses of mutants lacking these proteins. We present experimental results for the response of yeast cells to sharp, step-like variations in external $Ca^{++}$ concentrations. We analyze the properties of the model and use it to simulate the experimental conditions investigated. The model and experiments diverge more markedly in the case of mutants laking the Pmc1 protein. We discuss possible extensions of the model to address these findings.
Highlights
Studying the response to calcium stress is an important area of research as it naturally appears in many biologically relevant contexts, including fertilization of eggs and muscle contraction
We prove that the model is well behaved with respect to the crucial variables describing the production of new proteins mediated by Crz1p and calcineurin
The near identical response of the wild and PMC1 deletion indicates a quantitatively small role of Pmc1p in the regulatory network, while it is the dominant term in the model. Another issue is the experimentally observed longer decay time for VCX1 deletion. This points to the fact that Pmr1p and Pmc1p must be first produced in larger numbers by the cell to assist in regulation, and this process requires a relatively long time
Summary
Studying the response to calcium stress is an important area of research as it naturally appears in many biologically relevant contexts, including fertilization of eggs and muscle contraction. Calcium is necessary for a wide variety of enzymatic functions and is used as a cellular messenger. Too much calcium in the cell can lead to hyperosmolarity, which changes the cellular ion concentrations and pH and is detrimental to most cellular functions. Cells must carefully control their cellular calcium, extracellular calcium may vary widely. The budding Saccharomyces cerevisiae has been used for over forty years as a model organism for a wide variety of cellular processes. S. cerevisiae responds to extracellular signals with changes in intracellular chemistry and gene expression. In this yeast, researchers have been able to develop many genetic methods for easy analysis, such as the ability to quickly delete, add, or move genes of interest [5]
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