Regulation of Hyphal Growth and N-Acetylglucosamine Catabolism by Two Transcription Factors in Candida albicans
Regulation of Hyphal Growth and N-Acetylglucosamine Catabolism by Two Transcription Factors in Candida albicans
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DOI：
10.1534/genetics.117.201491
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发表时间：
2017-05-01
期刊：
影响因子：
3.3
通讯作者：
Konopka, James B.
中科院分区：
文献类型：
--
作者：
Naseem, Shamoon;Min, Kyunghun;Konopka, James B.
氨基糖n -乙酰氨基葡萄糖（GlcNAc）除了在细胞表面具有众所周知的结构作用外，越来越被认为是一种重要的信号分子。在人类真菌病原体白色念珠菌中，GlcNAc刺激了几种反应，包括诱导其分解代谢所需的基因和从出芽到丝状菌丝生长的转换。我们鉴定了两个GlcNAc生长所需的基因（RON1和NGS1），发现缺乏这些基因的突变体不能诱导GlcNAc分解代谢所需的基因。NGS1对其他糖（如麦芽糖）的生长也很重要，但RON1似乎对GlcNAc有特异性。这两种突变体都可以在不可发酵的碳源上生长，这表明它们不影响线粒体功能，我们发现线粒体功能对GlcNAc上的生长很重要，但对GlcNAc诱导菌丝形态发生并不重要。有趣的是，ron1 Delta和ngs1 Delta突变体在对GlcNAc的反应中都存在菌丝形成缺陷，尽管GlcNAc分解代谢并不需要诱导菌丝形态发生。ron1 δ突变体在形成菌丝方面显示出部分缺陷，这是令人惊讶的，因为它在非诱导条件下显示出丝状细胞的水平升高。ron1 δ突变体也显示出在菌丝生长过程中通常上调的基因的基础表达水平升高。与此相一致的是，Ron1含有ndt80样dna结合域，表明它调节基因表达。因此，Ron1是GlcNAc反应途径的关键新组分，既是菌丝形态发生的激活因子，也是抑制因子。
The amino sugar N-acetylglucosamine (GlcNAc) is increasingly recognized as an important signaling molecule in addition to its well-known structural roles at the cell surface. In the human fungal pathogen Candida albicans, GlcNAc stimulates several responses including the induction of the genes needed for its catabolism and a switch from budding to filamentous hyphal growth. We identified two genes needed for growth on GlcNAc (RON1 and NGS1) and found that mutants lacking these genes fail to induce the genes needed for GlcNAc catabolism. NGS1 was also important for growth on other sugars, such as maltose, but RON1 appeared to be specific for GlcNAc. Both mutants could grow on nonfermentable carbon sources indicating that they do not affect mitochondrial function, which we show is important for growth on GlcNAc but not for GlcNAc induction of hyphal morphogenesis. Interestingly, both the ron1 Delta and ngs1 Delta mutants were defective in forming hyphae in response to GlcNAc, even though GlcNAc catabolism is not required for induction of hyphal morphogenesis. The ron1 Delta mutant showed a partial defect in forming hyphae, which was surprising since it displayed an elevated level of filamentous cells under noninducing conditions. The ron1 Delta mutant also displayed an elevated basal level of expression of genes that are normally upregulated during hyphal growth. Consistent with this, Ron1 contains an Ndt80-like DNA-binding domain, indicating that it regulates gene expression. Thus, Ron1 is a key new component of the GlcNAc response pathway that acts as both an activator and a repressor of hyphal morphogenesis.