Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
PLoS Pathog. 2010 Feb 5;6(2):e1000752. doi: 10.1371/journal.ppat.1000752.
Protein kinases play key roles in signaling and response to changes in the external environment. The ability of Candida albicans to quickly sense and respond to changes in its environment is key to its survival in the human host. Our guiding hypothesis was that creating and screening a set of protein kinase mutant strains would reveal signaling pathways that mediate stress response in C. albicans. A library of protein kinase mutant strains was created and screened for sensitivity to a variety of stresses. For the majority of stresses tested, stress response was largely conserved between C. albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. However, we identified eight protein kinases whose roles in cell wall regulation (CWR) were not expected from functions of their orthologs in the model fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. Analysis of the conserved roles of these protein kinases indicates that establishment of cell polarity is critical for CWR. In addition, we found that septins, crucial to budding, are both important for surviving and are mislocalized by cell wall stress. Our study shows an expanded role for protein kinase signaling in C. albicans cell wall integrity. Our studies suggest that in some cases, this expansion represents a greater importance for certain pathways in cell wall biogenesis. In other cases, it appears that signaling pathways have been rewired for a cell wall integrity response.
蛋白激酶在信号转导和对外界环境变化的反应中起着关键作用。白念珠菌快速感知和响应环境变化的能力是其在人体宿主中生存的关键。我们的指导假设是，创建和筛选一组蛋白激酶突变株，将揭示介导白念珠菌应激反应的信号通路。创建了一个蛋白激酶突变株文库，并对其进行了各种应激敏感性的筛选。对于大多数测试的应激，白念珠菌、酿酒酵母和裂殖酵母之间的应激反应在很大程度上是保守的。然而，我们鉴定了八个蛋白激酶，它们在细胞壁调节（CWR）中的作用与其在模式真菌酿酒酵母和裂殖酵母中的同源物的功能不相符。这些蛋白激酶保守作用的分析表明，建立细胞极性对于 CWR 至关重要。此外，我们发现，对于出芽至关重要的隔膜蛋白在细胞壁应激时不仅会错误定位，而且对于生存也是必需的。我们的研究表明，蛋白激酶信号在白念珠菌细胞壁完整性中具有扩展作用。我们的研究表明，在某些情况下，这种扩展代表了细胞壁生物发生中某些途径的重要性增加。在其他情况下，信号通路似乎已经为细胞壁完整性反应重新布线。
