title: Positive feedback regulates switching of phosphate transporters in S. cerevisiae.
abstract: The regulation of transporters by nutrient-responsive signaling pathways allows cells to tailor nutrient uptake to environmental conditions. We investigated the role of feedback generated by transporter regulation in the budding yeast phosphate-responsive signal transduction (PHO) pathway. Cells starved for phosphate activate feedback loops that regulate high- and low-affinity phosphate transport. We determined that positive feedback is generated by PHO pathway-dependent upregulation of Spl2, a negative regulator of low-affinity phosphate uptake. The interplay of positive and negative feedback loops leads to bistability in phosphate transporter usage--individual cells express predominantly either low- or high-affinity transporters, both of which can yield similar phosphate uptake capacity. Cells lacking the high-affinity transporter, and associated negative feedback, exhibit phenotypes that arise from hysteresis due to unopposed positive feedback. In wild-type cells, population heterogeneity generated by feedback loops may provide a strategy for anticipating changes in environmental phosphate levels.
authors: Howard Hughes Medical Institute, FAS Center for Systems Biology, Harvard University, 7 Divinity Avenue, Bauer 307, Cambridge, MA 02138, USA.
authors: Dennis D
authors: DD
authors: Wykoff
authors: Abbas H
authors: AH
authors: Rizvi
authors: Jonathan M
authors: JM
authors: Raser
authors: Brian
authors: B
authors: Margolin
authors: Erin K
authors: EK
authors: O'Shea
mesh_terms: D001692:Biological Transport; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D025461:Feedback, Physiological; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D028081:Proton-Phosphate Symporters / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C105495:PHO84 protein, S cerevisiae; D028061:Phosphate Transport Proteins; D028081:Proton-Phosphate Symporters; C111070:SPL2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins