Oscillatory stress stimulation uncovers an Achilles' heel of the yeast MAPK signaling network.
Oscillatory stress stimulation uncovers an Achilles' heel of the yeast MAPK signaling network.
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振荡应激刺激揭示了酵母 MAPK 信号网络的致命弱点。
DOI：
10.1126/science.aab0892
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发表时间：
2015-12-11
期刊：
影响因子：
--
通讯作者：
Lim WA
中科院分区：
文献类型：
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作者：
Mitchell A;Wei P;Lim WA
细胞必须解释经常随时间变化的环境信息。我们系统地监测了不同频率的振荡渗透胁迫下酵母细胞的生长情况。在特定的共振频率下，细胞的生长受到严重抑制，在这种频率下，细胞表现出过度激活的转录应激反应。这种行为代表了一种感觉上的误解——细胞错误地将振荡解释为渗透压不断增加的阶梯。这种误解是由于渗透压感应激酶网络在连续渗透胁迫下重新触发的能力。尽管这一特性对于应对自然挑战（如不断增加的渗透压）至关重要，但它会导致对与重新触发时间相匹配的非自然振荡输入的脆弱性进行权衡。这些发现证明了非自然动态扰动在揭示细胞调节网络的隐藏敏感性方面的价值。
Cells must interpret environmental information that often changes over time. We systematically monitored 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 kinase network to retrigger with sequential osmotic stresses. Although this feature is critical for coping with natural challenges — like continually increasing osmolarity — it results in a tradeoff 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.