Thomas Melissa R, O'Shea Erin K
Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.
Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9565-70. doi: 10.1073/pnas.0501122102. Epub 2005 Jun 22.
To survive in a dynamic and unpredictable environment, cells must correctly interpret and integrate extracellular signals with internal factors. In particular, internal stores of nutrients must be managed for use during periods of nutrient limitation. To gain insight into this complex process, we combined biochemical and spectroscopic techniques to follow the dynamics of the phosphate responsive signaling pathway in both single yeast cells and populations. We demonstrate that the phosphate-responsive genes PHO5 and PHO84 exhibit different kinetics of transcriptional induction in response to phosphate starvation, and that transient phosphate limitation causes induction of PHO84 but not PHO5. This differential kinetic behavior is largely eliminated in cells that lack the ability to store phosphate internally in the form of polyphosphate, but the threshold of external phosphate required for induction of PHO5 and PHO84 is unaffected. Our observations indicate that polyphosphate acts as a buffer that can be mobilized during periods of phosphate limitation and enables the phosphate-responsive signaling pathway to filter transient fluctuations in extracellular phosphate levels.
为了在动态且不可预测的环境中生存,细胞必须正确解读细胞外信号并将其与内部因素整合。特别是,必须管理内部营养物质储备,以便在营养限制时期使用。为深入了解这一复杂过程,我们结合了生化和光谱技术,追踪单个酵母细胞及群体中磷酸盐响应信号通路的动态变化。我们证明,磷酸盐响应基因PHO5和PHO84在响应磷酸盐饥饿时表现出不同的转录诱导动力学,并且短暂的磷酸盐限制会导致PHO84而非PHO5的诱导。这种不同的动力学行为在缺乏以多聚磷酸盐形式在内部储存磷酸盐能力的细胞中基本消除,但诱导PHO5和PHO84所需的外部磷酸盐阈值不受影响。我们的观察结果表明,多聚磷酸盐起到一种缓冲剂的作用,在磷酸盐限制时期可以被动员,使磷酸盐响应信号通路能够过滤细胞外磷酸盐水平的短暂波动。