title: Oscillatory stress stimulation uncovers an Achilles' heel of the yeast MAPK signaling network.
abstract: Cells must interpret environmental information that often changes over time. In our experiment, we systematically monitored the growth of yeast cells under various frequencies of oscillating osmotic stress. Growth was severely inhibited at a particular resonance frequency, at which cells show hyperactivated transcriptional stress responses. This behavior represents a sensory misperception: The cells incorrectly interpret oscillations as a staircase of ever-increasing osmolarity. The misperception results from the capacity of the osmolarity-sensing mitogen-activated protein kinase (MAPK) network to retrigger with sequential osmotic stresses. Although this feature is critical for coping with natural challenges, such as continually increasing osmolarity, it results in a trade-off of fragility to non-natural oscillatory inputs that match the retriggering time. These findings demonstrate the value of non-natural dynamic perturbations in exposing hidden sensitivities of cellular regulatory networks.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA. Center for Systems and Synthetic Biology, UCSF, San Francisco, CA 94158, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Mitchell
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA. Center for Quantitative Biology, and Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing 100871, China. lim@cmp.ucsf.edu pwei@pku.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA. Center for Systems and Synthetic Biology, UCSF, San Francisco, CA 94158, USA. Howard Hughes Medical Institute (HHMI), UCSF, San Francisco, CA 94158, USA. lim@cmp.ucsf.edu pwei@pku.edu.cn.
authors.forename: Wendell A
authors.initials: WA
authors.lastname: Lim
mesh_terms: D004252:DNA Mutational Analysis; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008962:Models, Theoretical; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D020928:Mitogen-Activated Protein Kinases