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首页> 外文期刊>Journal of bacteriology >Molecular and Phenotypic Analysis of CaVRG4, Encoding an Essential Golgi Apparatus GDP-Mannose Transporter
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Molecular and Phenotypic Analysis of CaVRG4, Encoding an Essential Golgi Apparatus GDP-Mannose Transporter

机译：CaVRG4的分子和表型分析，编码必需的高尔基体GDP-甘露糖转运蛋白。

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Cell surface mannan is implicated in almost every aspect of pathogenicity of Candida albicans. In Saccharomyces cerevisiae, the Vrg4 protein acts as a master regulator of mannan synthesis through its role in substrate provision. The substrate for mannosylation of proteins and lipids in the Golgi apparatus is GDP-mannose, whose lumenal transport is catalyzed by Vrg4p. This nucleotide sugar is synthesized in the cytoplasm by pathways that are highly conserved in all eukaryotes, but its lumenal transport (and hence Golgi apparatus-specific mannosylation) is a fungus-specific process. To begin to study the role of Golgi mannosylation in C. albicans, we isolated the CaVRG4 gene and analyzed the effects of loss of its function. CaVRG4 encodes a functional homologue of the S. cerevisiae GDP-mannose transporter. CaVrg4p localized to punctate spots within the cytoplasm of C. albicans in a pattern reminiscent of localization of Vrg4p in the Golgi apparatus in S. cerevisiae. Like partial loss of ScVRG4 function, partial loss of CaVRG4 function resulted in mannosylation defects, which in turn led to a number of cell wall-associated phenotypes. While heterozygotes displayed no growth phenotypes, a hemizygous strain, containing a single copy of CaVRG4 under control of the methionine-repressible MET3 promoter, did not grow in the presence of methionine and cysteine, demonstrating that CaVRG4 is essential for viability. Mutant Candida vrg4 strains were defective in hyphal formation but exhibited a constitutive polarized mode of pseudohyphal growth. Because the VRG4 gene is essential for yeast viability but does not have a mammalian homologue, it is a particularly attractive target for development of antifungal therapies.
机译：细胞表面甘露聚糖几乎参与了白色念珠菌的致病性研究。在酿酒酵母中，Vrg4蛋白通过其在底物供应中的作用而充当甘露聚糖合成的主要调节剂。高尔基体中蛋白质和脂质的甘露糖基化作用的底物是GDP-甘露糖，其腔内运输被Vrg4p催化。该核苷酸糖是通过在所有真核生物中高度保守的途径在细胞质中合成的，但是其腔运输（以及因此的高尔基体特异性甘露糖基化）是真菌特异性的过程。开始研究高尔基甘露糖基化在 C中的作用。 ，我们分离了 CaVRG4 基因，并分析了其功能丧失的影响。 CaVRG4 编码 S的功能同源物。酿酒酵母GDP-甘露糖转运蛋白。 CaVrg4p定位于 C细胞质内的点状斑点。白色念珠菌的模式让人联想到 S中高尔基体中Vrg4p的定位。啤酒酵母。与 ScVRG4 功能的部分丧失一样， CaVRG4 功能的部分丧失导致甘露糖基化缺陷，进而导致许多细胞壁相关的表型。尽管杂合子没有生长表型，但是在蛋氨酸存在下，半合子菌株在蛋氨酸可抑制的 MET3 启动子的控制下只包含一个单拷贝的 CaVRG4 。半胱氨酸，证明 CaVRG4 对生存能力至关重要。突变的 Candida vrg4 菌株在菌丝形成方面有缺陷，但表现出假菌丝生长的本构极化模式。因为 VRG4 基因对于酵母的生存能力至关重要，但是没有哺乳动物的同源物，所以它是开发抗真菌疗法特别有吸引力的靶标。

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