Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;
Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan.
Proc Natl Acad Sci U S A. 2017 May 23;114(21):E4149-E4157. doi: 10.1073/pnas.1702181114. Epub 2017 May 11.
Cell-cell signaling is subject to variability in the extracellular volume, cell number, and dilution that potentially increase uncertainty in the absolute concentrations of the extracellular signaling molecules. To direct cell aggregation, the social amoebae collectively give rise to oscillations and waves of cyclic adenosine 3',5'-monophosphate (cAMP) under a wide range of cell density. To date, the systems-level mechanism underlying the robustness is unclear. By using quantitative live-cell imaging, here we show that the magnitude of the cAMP relay response of individual cells is determined by fold change in the extracellular cAMP concentrations. The range of cell density and exogenous cAMP concentrations that support oscillations at the population level agrees well with conditions that support a large fold-change-dependent response at the single-cell level. Mathematical analysis suggests that invariance of the oscillations to density transformation is a natural outcome of combining secrete-and-sense systems with a fold-change detection mechanism.
细胞间信号传递受到细胞外体积、细胞数量和稀释度的变化的影响，这可能会增加细胞外信号分子的绝对浓度的不确定性。为了指导细胞聚集，社会性阿米巴虫在广泛的细胞密度下共同产生环腺苷酸 3'，5'-单磷酸（cAMP）的振荡和波。迄今为止，其稳健性的系统级机制尚不清楚。通过使用定量活细胞成像，我们在这里显示个体细胞中 cAMP 接力反应的幅度由细胞外 cAMP 浓度的变化倍数决定。在群体水平上支持振荡的细胞密度和外源性 cAMP 浓度范围与在单细胞水平上支持大的倍数变化依赖性反应的条件非常吻合。数学分析表明，对密度变换的振荡不变性是将分泌-感应系统与倍数变化检测机制相结合的自然结果。
