Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Sci Signal. 2020 May 19;13(632):eaay3585. doi: 10.1126/scisignal.aay3585.
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.
细胞可以存储先前经验的记忆，以调节它们对后续压力的反应，正如在酵母中观察到的蛋白激酶 A (PKA)介导的一般应激反应，它是抵抗未来应激条件所必需的。使用微流控和延时显微镜，我们定量分析了细胞对压力适应的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。短暂的记忆是由海藻糖合酶和海藻糖代谢介导的。长时记忆是由 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的。短期和长期记忆可以通过不同的启动输入动态选择性地诱导。计算模型揭示了 PKA 介导的调控网络如何将先前的刺激编码成具有不同动力学的记忆。这种双相记忆编码方案可能代表了一种在快速变化的环境中为未来挑战做准备的一般策略。
