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MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeast

机译：MAPK介导的酵母中双峰基因表达和自适应梯度传感

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摘要

The mating pathway in Saccharomyces cerevisiae has been the focus of considerable research effort, yet many quantitative aspects of its regulation still remain unknown. Using an integrated approach involving experiments in microfluidic chips and computational modelling, we studied gene expression and phenotypic changes associated with the mating response under well-defined pheromone gradients. Here we report a combination of switch-like and graded pathway responses leading to stochastic phenotype determination in a specific range of pheromone concentrations. Furthermore, we show that these responses are critically dependent on mitogen-activated protein kinase (MAPK)-mediated regulation of the activity of the pheromone-response-specific transcription factor, Ste12, as well as on the autoregulatory feedback of Ste12. In particular, both the switch-like characteristics and sensitivity of gene expression in shmooing cells to pheromone concentration were significantly diminished in cells lacking Kss1, one of the MAP kinases activated in the mating pathway. In addition, the dynamic range of gradient sensing of Kss1-deficient cells was reduced compared with wild type. We thus provide unsuspected functional significance for this kinase in regulation of the mating response.
机译：酿酒酵母中的交配途径一直是大量研究工作的重点，但其调控的许多定量方面仍然未知。使用涉及微流控芯片实验和计算建模的集成方法，我们研究了在明确的信息素梯度下与交配反应相关的基因表达和表型变化。在这里，我们报告的开关样和分级的路径反应的组合，导致在特定的信息素浓度范围内随机表型的确定。此外，我们表明，这些反应主要取决于信息素反应特异性转录因子Ste12的活性，由丝裂原激活的蛋白激酶（MAPK）介导的调节，以及Ste12的自调节反馈。尤其是，缺少Kss1的细胞（在交配途径中被激活的MAP激酶之一），smooing细胞中开关样特征和基因表达对信息素浓度的敏感性都大大降低了。此外，与野生型相比，Kss1缺陷细胞的梯度传感动态范围减小了。因此，我们为这种激酶在调控交配反应中提供了意想不到的功能意义。

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