Cells can store memories of prior experiences to modulate their responses to subsequent stresses, as seen for the protein kinase A (PKA)-mediated general stress response in yeast, which is required for resistance against future stressful conditions. Using microfluidics and time-lapse microscopy, we quantitatively analyzed how the cellular memory of stress adaptation is encoded in single yeast cells. We found that cellular memory was biphasic. Short-lived memory was mediated by trehalose synthase and trehalose metabolism. Long-lived memory was mediated by PKA-regulated stress-responsive transcription factors and cytoplasmic messenger ribonucleoprotein granules. Short- and long-lived memory could be selectively induced by different priming input dynamics. Computational modeling revealed how the PKA-mediated regulatory network could encode previous stimuli into memories with distinct dynamics. This biphasic memory-encoding scheme might represent a general strategy to prepare for future challenges in rapidly changing environments.

中文翻译：

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蛋白激酶 A 调节的网络编码短期和长期的细胞记忆。

细胞可以存储先前经历的记忆，以调节它们对后续压力的反应，如酵母中蛋白激酶 A (PKA) 介导的一般压力反应所见，这是抵抗未来压力条件所必需的。使用微流体和延时显微镜，我们定量分析了应激适应的细胞记忆是如何在单个酵母细胞中编码的。我们发现细胞记忆是双相的。短期记忆由海藻糖合酶和海藻糖代谢介导。长寿命记忆由 PKA 调节的应激反应转录因子和细胞质信使核糖核蛋白颗粒介导。不同的启动输入动态可以选择性地诱导短期和长期记忆。计算模型揭示了 PKA 介导的调节网络如何将先前的刺激编码到具有不同动态的记忆中。这种双相内存编码方案可能代表了一种通用策略，可以在快速变化的环境中为未来的挑战做好准备。