title: Simulating calcium influx and free calcium concentrations in yeast.
abstract: Yeast can proliferate in environments containing very high Ca(2+) primarily due to the activity of vacuolar Ca(2+) transporters Pmc1 and Vcx1. Yeast mutants lacking these transporters fail to grow in high Ca(2+) environments, but growth can be restored by small increases in environmental Mg(2+). Low extracellular Mg(2+) appeared to competitively inhibit novel Ca(2+) influx pathways and to diminish the concentration of free Ca(2+) in the cytoplasm, as judged from the luminescence of the photoprotein aequorin. These Mg(2+)-sensitive Ca(2+) influx pathways persisted in yvc1 cch1 double mutants. Based on mathematical models of the aequorin luminescence traces, we propose the existence in yeast of at least two Ca(2+) transporters that undergo rapid feedback inhibition in response to elevated cytosolic free Ca(2+) concentration. Finally, we show that Vcx1 helps return cytosolic Ca(2+) toward resting levels after shock with high extracellular Ca(2+) much more effectively than Pmc1 and that calcineurin, a protein phosphatase regulator of Vcx1 and Pmc1, had no detectable effects on these factors within the first few minutes of its activation. Therefore, computational modeling of Ca(2+) transport and signaling in yeast can provide important insights into the dynamics of this complex system.
authors.affiliation: Section Computational Science, Faculty of Science, University of Amsterdam, Kruislaan 403, 1098 SJ Amsterdam, The Netherlands. jcui@science.uva.nl
authors.forename: Jiangjun
authors.initials: J
authors.lastname: Cui
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Kaandorp
authors.forename: Olufisayo O
authors.initials: OO
authors.lastname: Ositelu
authors.forename: Veronica
authors.initials: V
authors.lastname: Beaudry
authors.forename: Alicia
authors.initials: A
authors.lastname: Knight
authors.forename: Yves F
authors.initials: YF
authors.lastname: Nanfack
authors.forename: Kyle W
authors.initials: KW
authors.lastname: Cunningham
mesh_terms: D002118:Calcium / Q000378:metabolism* / Q000633:toxicity; D020013:Calcium Signaling / Q000187:drug effects; D003198:Computer Simulation; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008274:Magnesium; D002118:Calcium
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