Positive feedback regulates switching of phosphate transporters in S-cerevisiae
Positive feedback regulates switching of phosphate transporters in S-cerevisiae
复制标题
DOI：
10.1016/j.molcel.2007.07.022
复制
发表时间：
2007-09-21
期刊：
影响因子：
16
通讯作者：
O'Shea, Erin K.
中科院分区：
文献类型：
--
作者：
Wykoff, Dennis D.;Rizvi, Abbas H.;O'Shea, Erin K.
通过营养响应信号通路对转运蛋白的调节使细胞能够根据环境条件调整营养吸收。我们研究了转运蛋白调节产生的反馈在芽殖酵母磷酸盐响应信号转导（PHO）途径中的作用。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。我们确定正反馈是由 PHO 途径依赖性 Sp12 上调产生的，Sp12 是低亲和力磷酸盐摄取的负调节因子。正反馈环路和负反馈环路的相互作用导致磷酸盐转运蛋白使用的双稳定性——个体细胞主要表达低亲和力转运蛋白或高亲和力转运蛋白，这两种转运蛋白都可以产生相似的磷酸盐摄取能力。缺乏高亲和力转运蛋白和相关负反馈的细胞表现出由于无对抗的正反馈而产生的滞后现象。在野生型细胞中，反馈回路产生的群体异质性可能提供预测环境磷酸盐水平变化的策略。
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 Sp12, 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.