Biosynthesis of the Fungal Cell Wall Polysaccharide Galactomannan Requires Intraluminal GDP-mannose
Biosynthesis of the Fungal Cell Wall Polysaccharide Galactomannan Requires Intraluminal GDP-mannose
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DOI：
10.1074/jbc.m112.398321
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发表时间：
2012-12-28
影响因子：
4.8
通讯作者：
Routier, Francoise H.
中科院分区：
文献类型：
--
作者：
Engel, Jakob;Schmalhorst, Philipp S.;Routier, Francoise H.
真菌细胞壁通常含有甘露糖和半乳糖的聚合物，称为半乳甘露聚糖。在致病性丝状真菌烟曲霉中，这种多糖由具有半乳呋喃侧链的线性甘露聚糖主链组成，并通过糖基磷脂酰肌醇锚定到质膜上或共价连接到细胞壁上。迄今为止，这种多糖的生物合成和意义是未知的。目前的数据表明，删除高尔基UDP-半乳呋喃糖转运蛋白GlfB或GDP-甘露糖转运蛋白GmtA分别导致半乳呋喃或半乳甘露聚糖的缺乏。这表明半乳甘露聚糖的生物合成可能发生在高尔基体的内腔中，因此与迄今为止研究的发生在质膜处的其他真菌细胞壁多糖的生物合成形成对比。假设半乳甘露聚糖从膜到细胞壁的转糖基化，因为细胞壁结合和膜结合的多糖形式在产生的突变体中受到影响。考虑到A.烟曲霉GmtA缺陷突变体，证明这种模式可能提供新的抗真菌治疗的目标。
Fungal cell walls frequently contain a polymer of mannose and galactose called galactomannan. In the pathogenic filamentous fungus Aspergillus fumigatus, this polysaccharide is made of a linear mannan backbone with side chains of galactofuran and is anchored to the plasma membrane via a glycosylphosphatidylinositol or is covalently linked to the cell wall. To date, the biosynthesis and significance of this polysaccharide are unknown. The present data demonstrate that deletion of the Golgi UDP-galactofuranose transporter GlfB or the GDP-mannose transporter GmtA leads to the absence of galactofuran or galactomannan, respectively. This indicates that the biosynthesis of galactomannan probably occurs in the lumen of the Golgi apparatus and thus contrasts with the biosynthesis of other fungal cell wall polysaccharides studied to date that takes place at the plasma membrane. Transglycosylation of galactomannan from the membrane to the cell wall is hypothesized because both the cell wall-bound and membrane-bound polysaccharide forms are affected in the generated mutants. Considering the severe growth defect of the A. fumigatus GmtA-deficient mutant, proving this paradigm might provide new targets for antifungal therapy.