Heat-stress triggers MAPK crosstalk to turn on the hyperosmotic response pathway.
Heat-stress triggers MAPK crosstalk to turn on the hyperosmotic response pathway.
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DOI：
10.1038/s41598-018-33203-6
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发表时间：
2018-10-11
影响因子：
4.6
通讯作者：
Colman-Lerner A
中科院分区：
文献类型：
--
作者：
Dunayevich P;Baltanás R;Clemente JA;Couto A;Sapochnik D;Vasen G;Colman-Lerner A
细胞根据外部和内部信号的组合做出决定。在酵母中，高渗透压反应（HOG）是一种丝裂原活化蛋白激酶（MAPK）途径，对各种刺激作出反应，并且是一般应激反应的中心。本文研究了热应激（HS）对HOG的影响。使用活细胞的报告和遗传学，我们表明，HS促进Hog 1磷酸化和Hog 1依赖的基因表达，完全通过Sln 1磷酸化分支，和激活的强度较大的酵母适应高外部渗透压。HS对HOG的刺激是间接的。首先，我们表明，HS导致甘油损失，HOG激活所必需的。通过删除甘油孔蛋白FPS 1或其调节剂RGC 1和ASK 10/RGC 2或通过增加外部甘油来防止甘油流出，大大降低了HOG激活。其次，我们发现HS对HOG的刺激依赖于第二条MAPK途径的运作，即细胞壁完整性（CWI），这是HS的一种众所周知的介导因子，因为失活Pkc 1或删除MAPK SLT 2大大降低了HOG的激活。我们的数据表明，在这个过程中的CWI的主要作用是刺激甘油损失。我们发现在表达组成型开放通道突变体（Fps 1-Δ11）的酵母中，HOG活性不依赖于Slt 2。总之，我们认为HS由于甘油和伴随的水的损失而导致膨压减少，这实际上是刺激HOG的原因。因此，总的来说，我们的研究结果突出了Fps 1和甘油代谢在酵母MAPK途径之间的通信中的核心作用，这对在不断变化的环境中生存和繁殖至关重要。
Cells make decisions based on a combination of external and internal signals. In yeast, the high osmolarity response (HOG) is a mitogen-activated protein kinase (MAPK) pathway that responds to a variety of stimuli, and it is central to the general stress response. Here we studied the effect of heat-stress (HS) on HOG. Using live-cell reporters and genetics, we show that HS promotes Hog1 phosphorylation and Hog1-dependent gene expression, exclusively via the Sln1 phosphorelay branch, and that the strength of the activation is larger in yeast adapted to high external osmolarity. HS stimulation of HOG is indirect. First, we show that HS causes glycerol loss, necessary for HOG activation. Preventing glycerol efflux by deleting the glyceroporin FPS1 or its regulators RGC1 and ASK10/RGC2, or by increasing external glycerol, greatly reduced HOG activation. Second, we found that HOG stimulation by HS depended on the operation of a second MAPK pathway, the cell-wall integrity (CWI), a well-known mediator of HS, since inactivating Pkc1 or deleting the MAPK SLT2 greatly reduced HOG activation. Our data suggest that the main role of the CWI in this process is to stimulate glycerol loss. We found that in yeast expressing the constitutively open channel mutant (Fps1-Δ11), HOG activity was independent of Slt2. In summary, we suggest that HS causes a reduction in turgor due to the loss of glycerol and the accompanying water, and that this is what actually stimulates HOG. Thus, taken together, our findings highlight a central role for Fps1, and the metabolism of glycerol, in the communication between the yeast MAPK pathways, essential for survival and reproduction in changing environments.
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影响因子：
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作者：
Gordon, Andrew;Colman-Lerner, Alejandro;Brent, Roger
通讯作者：
Brent, Roger
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LEVIN, DE
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作者：
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通讯作者：
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