The bZIP transcription factor Rca1p is a central regulator of a novel CO₂ sensing pathway in yeast.
The bZIP transcription factor Rca1p is a central regulator of a novel CO₂ sensing pathway in yeast.
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DOI：
10.1371/journal.ppat.1002485
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发表时间：
2012-01
期刊：
影响因子：
6.7
通讯作者：
Mühlschlegel FA
中科院分区：
文献类型：
--
作者：
Cottier F;Raymond M;Kurzai O;Bolstad M;Leewattanapasuk W;Jiménez-López C;Lorenz MC;Sanglard D;Váchová L;Pavelka N;Palková Z;Mühlschlegel FA
像许多生物一样，真菌病原体白色念珠菌感知环境CO2浓度的变化。这种反应涉及两种主要蛋白质：腺苷酸环化酶和碳酸酐酶（CA）。在这里，我们证明，CA的表达是严格控制的CO2的可用性和确定的bZIP转录因子Rca1p作为第一个CO2调节CA在酵母中的表达。我们发现，Rca1p上调CA表达与哺乳动物吞噬细胞接触过程中，并证明丝氨酸124是Rca1p信号，这是独立的腺苷酸环化酶发生的关键。ChIP芯片分析和鉴定Rca1p的直系同源物在模型酵母酿酒酵母（Cst6p）点的真菌中的这种新途径的广泛意义。通过使用先进的显微镜，我们第一次可视化了二氧化碳积累对整个真菌种群基因表达的影响，具有特殊的细节水平。我们的研究结果提出了bZIP蛋白Rca1p作为碳酸酐酶的第一个真菌调节剂，并揭示了在酵母中存在的腺苷酸环化酶独立的CO2传感途径。Rca1p似乎调节细胞代谢响应CO2的可用性在不同的环境中的吞噬体，酵母菌群或液体培养。皮肤感染、口腔和阴道鹅口疮或血流念珠菌病是由人类病原体白色念珠菌引起的一些疾病。感染小生境的高度通用性反映了这种酵母对环境中强烈变化（如CO2浓度）的反应能力。该分子启动了一种必需蛋白质的调节：碳酸酐酶，不是通过已知的腺苷酸环化酶CO2传感器，而是通过涉及转录调节因子Rca1p的新型真菌CO2传感途径发现的。该蛋白还与C.白色念珠菌。Rca1p在酿酒酵母中的直向同源物在低CO2浓度气氛中诱导碳酸酐酶中表现出保守的功能，这表明Rca1p在真菌CO2传感中具有广泛的意义。
Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO2 and identify the bZIP transcription factor Rca1p as the first CO2 regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO2 build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO2 sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO2 availability in environments as diverse as the phagosome, yeast communities or liquid culture. Skin infection, oral and vaginal thrush, or bloodstream candidiasis are some of the diseases caused by the human pathogen Candida albicans. The high versatility of infection niches reflects the capacity of this yeast to respond to strong variations in its environment such as CO2 concentration. This molecule initiates the regulation of an essential protein: carbonic anhydrase, not through the known adenylyl cyclase CO2 sensor but as we discovered via a novel fungal CO2 sensing pathway involving the transcriptional regulator Rca1p. This protein is additionally implicated in growth, yeast-to-hyphae morphological switch and cell wall stability of C. albicans. The ortholog of Rca1p in Saccharomyces cerevisiae demonstrated a conserved function in the induction of the carbonic anhydrase in low CO2 concentration atmospheres pointing to the broad significance of Rca1p in fungal CO2 sensing.
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影响因子：
3.2
作者：
Kovacikova, Gabriela;Lin, Wei;Skorupski, Karen
通讯作者：
Skorupski, Karen
影响因子：
--
作者：
Mogensen, EG;Janbon, G;Mühlschlegel, FA
通讯作者：
Mühlschlegel, FA
影响因子：
9.8
作者：
Lavoie H;Hogues H;Mallick J;Sellam A;Nantel A;Whiteway M
通讯作者：
Whiteway M
影响因子：
6.7
作者：
Hall RA;De Sordi L;Maccallum DM;Topal H;Eaton R;Bloor JW;Robinson GK;Levin LR;Buck J;Wang Y;Gow NA;Steegborn C;Mühlschlegel FA
通讯作者：
Mühlschlegel FA
影响因子：
14.9
作者：
Carlson JM;Chakravarty A;DeZiel CE;Gross RH
通讯作者：
Gross RH