Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity.
Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity.
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DOI：
10.1091/mbc.e12-06-0477
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发表时间：
2013-02
影响因子：
3.3
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Su C;Lu Y;Liu H
许多重要的菌丝发育的信号通路已被确定，但白念珠菌如何协调这些信号通路在菌丝发育过程中的信息仍然是一个主要的问题。结果表明，减少Tor 1信号降低了Hog 1 MAP激酶的基础活性，以维持菌丝伸长。白色念珠菌能够在酵母和菌丝形式之间发生可逆的形态学变化，以响应环境线索。这种形态可塑性是其发病机制所必需的。菌丝发育需要启动子染色质的两个时间上相关的变化，这是顺序调节的cAMP/蛋白激酶A激活后暂时清除转录抑制剂Nrg 1和启动子招募组蛋白脱乙酰酶Hda 1下减少雷帕霉素（Tor 1）信号的目标。加塔家族转录因子Brg 1将Hda 1募集到启动子中以维持菌丝发育，并且BRG 1表达是减少的Tor 1信号传导的读数。Tor 1如何调节BRG 1表达尚不清楚。使用正向遗传筛选的突变体，可以维持菌丝在丰富的媒体伸长，我们发现HOG丝裂原活化蛋白激酶途径的hog 1，ssk 2和pbs 2突变体表达BRG 1雷帕霉素无关。此外，雷帕霉素通过两种Hog 1酪氨酸磷酸酶Ptp 2和Ptp 3的功能降低Hog 1的基础活性。活性Hog 1通过转录抑制因子Sko 1抑制BRG 1的表达，因为Sko 1与Hog 1突变体或雷帕霉素中BRG 1的启动子分离。我们的数据表明，减少Tor 1信号降低Hog 1的基础活性，通过Hog 1磷酸酶激活BRG 1表达菌丝伸长。
Many signaling pathways important for hyphal development have been identified, but how Candida albicans coordinates information from these signaling pathways during hyphal development remains a major question. It is shown that reduced Tor1 signaling lowers the basal activity of the Hog1 MAP kinase to sustain hyphal elongation. Candida albicans is able to undergo reversible morphological changes between yeast and hyphal forms in response to environmental cues. This morphological plasticity is essential for its pathogenesis. Hyphal development requires two temporally linked changes in promoter chromatin, which is sequentially regulated by temporarily clearing the transcription inhibitor Nrg1 upon activation of cAMP/protein kinase A and promoter recruitment of the histone deacetylase Hda1 under reduced target of rapamycin (Tor1) signaling. The GATA family transcription factor Brg1 recruits Hda1 to promoters for sustained hyphal development, and BRG1 expression is a readout of reduced Tor1 signaling. How Tor1 regulates BRG1 expression is not clear. Using a forward genetic screen for mutants that can sustain hyphal elongation in rich media, we found hog1, ssk2, and pbs2 mutants of the HOG mitogen-activated protein kinase pathway to express BRG1 irrespective of rapamycin. Furthermore, rapamycin lowers the basal activity of Hog1 through the functions of the two Hog1 tyrosine phosphatases Ptp2 and Ptp3. Active Hog1 represses the expression of BRG1 via the transcriptional repressor Sko1 as Sko1 disassociates from the promoter of BRG1 in the hog1 mutant or in rapamycin. Our data suggest that reduced Tor1 signaling lowers Hog1 basal activity via Hog1 phosphatases to activate BRG1 expression for hyphal elongation.