Candida albicans Ume6, a Filament-Specific Transcriptional Regulator, Directs Hyphal Growth via a Pathway Involving Hgc1 Cyclin-Related Protein
Candida albicans Ume6, a Filament-Specific Transcriptional Regulator, Directs Hyphal Growth via a Pathway Involving Hgc1 Cyclin-Related Protein
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DOI：
10.1128/ec.00046-10
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发表时间：
2010-09-01
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影响因子：
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通讯作者：
Kadosh, David
中科院分区：
文献类型：
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作者：
Carlisle, Patricia L.;Kadosh, David
白色念珠菌是最常见的人类真菌病原体，其从酵母菌转变为菌丝的能力对于致病性至关重要。虽然已经鉴定和表征了多种对表达起重要作用的转录因子，但C.白色念珠菌的形态发生和驱动菌丝生长的分子机制还没有很好的定义。我们以前已经观察到，UME6，它编码一个有害生物特异性的转录调节因子的组成型表达，是足以直接菌丝生长的情况下，有害生物诱导的条件。在这里，我们表明，HGC 1，编码的细胞周期蛋白相关的蛋白质的必要条件下诱导的菌丝生长，是特别重要的琼脂入侵，菌丝的延伸，并形成真正的隔膜，在非丝诱导条件下组成型UME6表达。HGC 1依赖性的Rga 2，Cdc42 GT3激活蛋白（GAP）的失活，似乎也是重要的这些过程。响应于毒性诱导条件，HGC 1在UME 6之前被诱导，尽管UME 6控制HGC 1表达的水平和持续时间，这可能对菌丝延伸很重要。有趣的是，上位性分析表明，UME 6和HGC 1在早期纤维形成过程中发挥不同的作用。这些研究结果建立了一个关键的调节子之间的联系和下游机制的菌丝形成的重要。此外，这项研究表明，一个组成型表达高水平的UME 6的菌株提供了一个强大的战略，具体剖析下游机制的重要菌丝发育的复杂的诱导条件下。
The ability of Candida albicans, the most common human fungal pathogen, to transition from yeast to hyphae is essential for pathogenicity. While a variety of transcription factors important for filamentation have been identified and characterized, links between transcriptional regulators of C. albicans morphogenesis and molecular mechanisms that drive hyphal growth are not well defined. We have previously observed that constitutive expression of UME6, which encodes a filament-specific transcriptional regulator, is sufficient to direct hyphal growth in the absence of filament-inducing conditions. Here we show that HGC1, encoding a cyclin-related protein necessary for hyphal growth under filament-inducing conditions, is specifically important for agar invasion, hyphal extension, and formation of true septa in response to constitutive UME6 expression under non-filament-inducing conditions. HGC1-dependent inactivation of Rga2, a Cdc42 GTPase activating protein (GAP), also appears to be important for these processes. In response to filament-inducing conditions, HGC1 is induced prior to UME6 although UME6 controls the level and duration of HGC1 expression, which are likely to be important for hyphal extension. Interestingly, an epistasis analysis suggests that UME6 and HGC1 play distinct roles during early filament formation. These findings establish a link between a key regulator of filamentation and a downstream mechanism important for hyphal formation. In addition, this study demonstrates that a strain expressing constitutive high levels of UME6 provides a powerful strategy to specifically dissect downstream mechanisms important for hyphal development in the absence of complex filament-inducing conditions.