Wykoff Dennis D, Rizvi Abbas H, Raser Jonathan M, Margolin Brian, O'Shea Erin K
Howard Hughes Medical Institute, FAS Center for Systems Biology, Harvard University, 7 Divinity Avenue, Bauer 307, Cambridge, MA 02138, USA.
Mol Cell. 2007 Sep 21;27(6):1005-13. doi: 10.1016/j.molcel.2007.07.022.
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.
营养物响应信号通路对转运蛋白的调控使细胞能够根据环境条件调整营养物摄取。我们研究了转运蛋白调控产生的反馈在出芽酵母磷酸盐响应信号转导（PHO）通路中的作用。缺乏磷酸盐的细胞会激活调节高亲和力和低亲和力磷酸盐转运的反馈回路。我们确定，低亲和力磷酸盐摄取的负调节因子Spl2的PHO通路依赖性上调产生了正反馈。正负反馈回路的相互作用导致了磷酸盐转运蛋白使用的双稳态——单个细胞主要表达低亲和力或高亲和力转运蛋白，两者都能产生相似的磷酸盐摄取能力。缺乏高亲和力转运蛋白及相关负反馈的细胞表现出因无对抗正反馈导致的滞后现象所产生的表型。在野生型细胞中，反馈回路产生的群体异质性可能为预测环境磷酸盐水平的变化提供一种策略。
