Activation of signaling pathways related to cell wall integrity and multidrug resistance by organic solvent in Saccharomyces cerevisiae
Activation of signaling pathways related to cell wall integrity and multidrug resistance by organic solvent in Saccharomyces cerevisiae
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DOI：
10.1007/s00294-013-0419-5
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发表时间：
2013-12
期刊：
影响因子：
2.5
通讯作者：
N. Nishida;Dongyu Jing;K. Kuroda;M. Ueda
中科院分区：
文献类型：
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作者：
N. Nishida;Dongyu Jing;K. Kuroda;M. Ueda
有机溶剂对活细胞有毒。在真核生物中，只有酿酒酵母（Saccharomyces cerevisiae）具有有机溶剂耐受性。虽然在以前的研究中已经确定了几个有助于有机溶剂耐受性的因素，但酵母细胞如何自然地响应有机溶剂胁迫的机制尚不清楚。我们证明了多效性耐药（PDR）途径有助于响应有机溶剂胁迫。通过转录因子Pdr1p和Pdr3p中的突变激活PDR途径导致有机溶剂耐受性。暴露于有机溶剂也诱导转录水平的PDR5，它编码一个主要的药物外排泵。Pdr5p的过量生产提高了有机溶剂耐受性，可能是通过将有机溶剂排出细胞。此外，我们还发现，有机溶剂诱导细胞壁完整性（CWI）途径上调编码细胞壁相关蛋白Wsc3p和YnL190wp的基因，而WSC3和YNL190W的上调与PDR途径无关。在CWI途径的组分中，细胞表面传感器（Wsc3p和Mid2p）和转录因子（Swi4p和Swi6p）似乎特别参与对有机溶剂的响应。我们的研究结果表明，S.激活两种不同的信号通路，PDR通路和CWI通路，以科普来自有机溶剂的压力。
Organic solvents are toxic to living cells. In eukaryotes, cells with organic solvent tolerance have only been found inSaccharomyces cerevisiae. Although several factors contributing to organic solvent tolerance have been identified in previous studies, the mechanism of how yeast cells naturally respond to organic solvent stress is not known. We demonstrated that the pleiotropic drug resistance (PDR) pathway contributed to response to organic solvent stress. Activation of the PDR pathway by mutations in the transcription factors Pdr1p and Pdr3p led to organic solvent tolerance. Exposure to organic solvents also induced transcription levels ofPDR5, which encodes a major drug efflux pump. Overproduction of Pdr5p improved organic solvent tolerance, presumably by exporting organic solvents out of the cell. In addition, we showed that the cell wall integrity (CWI) pathway was induced in response to organic solvents to upregulate genes encoding the cell wall-related proteins Wsc3p and Ynl190wp.WSC3andYNL190Wwere upregulated independently of the PDR pathway. Among the components of the CWI pathway, the cell surface sensors (Wsc3p and Mid2p) and the transcription factors (Swi4p and Swi6p) appeared to be particularly involved in the response to organic solvents. Our findings indicate thatS. cerevisiaeactivates two different signaling pathways, the PDR pathway and the CWI pathway, to cope with stresses from organic solvents.