Positive Feedback Regulates Switching of Phosphate Transporters in S. cerevisiae

• DOI: 10.1016/j.molcel.2007.07.022
• Publication Date: 2007-09-21T11:13:34Z
• Authors: Dennis D. Wykoff; Abbas H. Rizvi; Jonathan M. Raser; Brian Margolin; Erin K. O'Shea
• Keywords: Positive feedback; Bistability; Negative feedback

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.