A Protein Kinase A-Regulated Network Encodes Short- and Long-Lived Cellular Memory

In plants, bacteria, flies, and even humans, prior exposure to a previous mild stress allows the system to adapt better to a severe stress in the future, indicating that the concept of a “cellular memory” of previous stressful events might be a general feature of biological systems. In yeast, the protein kinase A (PKA)-mediated general stress response functions to respond to and store memories of prior stress exposure, which is required for resistance against future stressful conditions. Using microfluidics and time-lapse microscopy, we analyzed how cellular memory of stress adaptation is dynamically encoded in single yeast cells. We found that the memory effect on future stress adaptation is biphasic, consisting of a short-lived component mediated by trehalose metabolism and a long-lasting component mediated by a transcriptional response and stabilized by messenger ribonucleoprotein granules. These two components could be selectively induced by different dynamics of priming inputs. Computational modeling further revealed how the PKA-mediated regulatory network could encode the information of previous stimuli into distinct memory dynamics. This biphasic memory-encoding scheme, analogous to innate and adaptive immune responses in mammals, might represent a general strategy to prepare for future challenges in rapidly changing environments