A Single UDP-galactofuranose Transporter Is Required for Galactofuranosylation in Aspergillus fumigatus
A Single UDP-galactofuranose Transporter Is Required for Galactofuranosylation in Aspergillus fumigatus
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DOI：
10.1074/jbc.m109.070219
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发表时间：
2009-12-04
影响因子：
4.8
通讯作者：
Routier, Francoise H.
中科院分区：
文献类型：
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作者：
Engel, Jakob;Schmalhorst, Philipp S.;Routier, Francoise H.
已经描述了在几种真核生物的细胞表面含有半乳糖呋喃糖（Galf）的分子，并且显示其有助于寄生虫硕大利什曼原虫和真菌烟曲霉的毒力。预计许多表面糖缀合物如N-聚糖或糖脂在高尔基体中被半乳糖呋喃糖基化。这就提出了一个问题，即在胞质溶胶中合成的呋喃半乳糖基化反应底物UDP-Galf如何易位到分泌途径的细胞器中。在这里，我们报告的第一个识别高尔基体本地化的核苷酸糖转运蛋白，命名为GlfB，特异性的UDP-半乳糖醛酸。体外转运试验建立了UDP-Galf与GlfB的结合，并排除了几种其他核苷酸糖的转运。此外，还探讨了glfB在A.烟曲霉糖缀合物和半乳甘露聚糖通过靶向基因缺失方法证明。我们的数据揭示了半乳甘露聚糖和分泌途径的细胞器之间的直接联系，这强烈表明细胞壁结合的多糖来源于其糖基磷脂酰肌醇锚定形式。
Galactofuranose (Galf) containing molecules have been described at the cell surface of several eukaryotes and shown to contribute to the virulence of the parasite Leishmania major and the fungus Aspergillus fumigatus. It is anticipated that a number of the surface glycoconjugates such as N-glycans or glycolipids are galactofuranosylated in the Golgi apparatus. This raises the question of how the substrate for galactofuranosylation reactions, UDP-Galf, which is synthesized in the cytosol, translocates into the organelles of the secretory pathway. Here we report the first identification of a Golgi-localized nucleotide sugar transporter, named GlfB, with specificity for a UDP-Galf. In vitro transport assays established binding of UDP-Galf to GlfB and excluded transport of several other nucleotide sugars. Furthermore, the implication of glfB in the galactofuranosylation of A. fumigatus glycoconjugates and galactomannan was demonstrated by a targeted gene deletion approach. Our data reveal a direct connection between galactomannan and the organelles of the secretory pathway that strongly suggests that the cell wall-bound polysaccharide originates from its glycosylphosphatidylinositol-anchored form.