Positive Feedback Regulates Switching of Phosphate Transporters in S. cerevisiae
- 1 September 2007
- journal article
- research article
- Published by Elsevier BV in Molecular Cell
- Vol. 27 (6), 1005-1013
- https://doi.org/10.1016/j.molcel.2007.07.022
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.Keywords
Funding Information
- Howard Hughes Medical Institute
- National Institutes of Health (GM51377)
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