Regulation of sugar transport and metabolism by the Candida albicans Rgt1 transcriptional repressor
Regulation of sugar transport and metabolism by the Candida albicans Rgt1 transcriptional repressor
复制标题
白色念珠菌 Rgt1 转录抑制因子对糖转运和代谢的调节
作者：
J. Sexton;V. Brown;M. Johnston
真菌病原体白色念珠菌引起全身感染的能力部分取决于Hgt 4的功能，Hgt 4是一种细胞表面糖传感器。Hgt 4在酿酒酵母中的直向同源物Snf 3和Rgt 2启动信号级联，使Rgt 1失活，Rgt 1是编码己糖转运蛋白的基因的转录阻遏物。为了确定Hgt 4是否通过C.白念珠菌Rgt 1的直系同源物，我们分析了Cargt 1缺失突变体。我们发现Cargt 1突变体对葡萄糖类似物2-脱氧葡萄糖敏感，这可能是由于编码葡萄糖转运蛋白的基因表达不受控制所致。事实上，转录谱显示，在没有糖的情况下，大约24个基因（包括编码己糖转运蛋白的多个HGT基因）的表达在Cargt 1突变体中增加，这表明CaRgt 1在这种条件下抑制了几个HGT基因的表达。一些HGT基因（可能编码高亲和力转运蛋白）也受到高水平葡萄糖的抑制，我们表明这种抑制是由CaMig 1介导的，CaMig 1是S.酿酒酵母，但不是由其partial CaMig 2。因此，CaRgt 1和CaMig 1协同调控C.白念珠菌己糖转运蛋白对不同水平的糖的反应。我们惊奇地发现CaRgt 1也调节GAL 1的表达，这表明在C.白色念珠菌是非常规的。最后，Cargt 1突变导致细胞超丝，并抑制hgt 4突变体的低表达表型，表明Hgt 4葡萄糖传感器可能通过CaRgt 1调节糖的输入和代谢来影响表达。版权所有© 2007约翰威利父子有限公司。
The ability of the fungal pathogen Candida albicans to cause systemic infections depends in part on the function of Hgt4, a cell surface sugar sensor. The orthologues of Hgt4 in Saccharomyces cerevisiae, Snf3 and Rgt2, initiate a signalling cascade that inactivates Rgt1, a transcriptional repressor of genes encoding hexose transporters. To determine whether Hgt4 functions similarly through the C. albicans orthologue of Rgt1, we analysed Cargt1 deletion mutants. We found that Cargt1 mutants are sensitive to the glucose analogue 2‐deoxyglucose, a phenotype probably due to uncontrolled expression of genes encoding glucose transporters. Indeed, transcriptional profiling revealed that expression of about two dozen genes, including multiple HGT genes encoding hexose transporters, is increased in the Cargt1 mutant in the absence of sugars, suggesting that CaRgt1 represses expression of several HGT genes under this condition. Some of the HGT genes (probably encoding high‐affinity transporters) are also repressed by high levels of glucose, and we show that this repression is mediated by CaMig1, the orthologue of the major glucose‐activated repressor in S. cerevisiae, but not by its paralogue CaMig2. Therefore, CaRgt1 and CaMig1 collaborate to control expression of C. albicans hexose transporters in response to different levels of sugars. We were surprised to find that CaRgt1 also regulates expression of GAL1, suggesting that regulation of galactose metabolism in C. albicans is unconventional. Finally, Cargt1 mutations cause cells to hyperfilament, and suppress the hypofilamented phenotype of an hgt4 mutant, indicating that the Hgt4 glucose sensor may affect filamentation by modulating sugar import and metabolism via CaRgt1. Copyright © 2007 John Wiley & Sons, Ltd.
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影响因子：
3.3
作者：
D. Irwin;W. Fonzi;D. Ho;S. Sag
通讯作者：
D. Irwin;W. Fonzi;D. Ho;S. Sag
影响因子：
3.9
作者：
Johnston, M;Kim, JH
通讯作者：
Kim, JH
影响因子：
1.5
作者：
M. Uhl;A. D. Johnson;M. Uhl;A. D. Johnson;Larry Mckay;Doug Kellogg
通讯作者：
M. Uhl;A. D. Johnson;M. Uhl;A. D. Johnson;Larry Mckay;Doug Kellogg
影响因子：
3.3
作者：
Flick, KM;Spielewoy, N;Wittenberg, C
通讯作者：
Wittenberg, C
DOI：
10.1073/pnas.0305901101
发表时间：
2004-02-10
影响因子：
11.1
作者：
Moriya, H;Johnston, M
通讯作者：
Johnston, M