State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, A-1190, Austria.
Sci Rep. 2019 Apr 10;9(1):5857. doi: 10.1038/s41598-019-42344-1.
In fungi many proteins, which play important roles in maintaining the function of the cell wall and participating in pathogenic processes, are anchored to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. It has been known that modification and removal of phosphoethanolamine (EtN-P) on the second mannose residue in GPI anchors is important for maturation and sorting of GPI anchored proteins in yeast and mammalian cells, but is a step absent from some protist parasites. In Aspergillus fumigatus, an opportunistic fungal pathogen causing invasive aspergillosis in humans, GPI-anchored proteins are known to be involved in cell wall synthesis and virulence. In this report the gene encoding A. fumigatus EtN-P transferase GPI7 was investigated. By deletion of the gpi7 gene, we evaluated the effects of EtN-P modification on the morphogenesis of A. fumigatus and localization of GPI proteins. Our results showed that deletion of the gpi7 gene led to reduced cell membrane GPI anchored proteins, the mis-localization of the cell wall GPI anchored protein Mp1, abnormal polarity, and autophagy in A. fumigatus. Our results suggest that addition of EtN-P of the second mannose on the GPI anchor is essential for transportation and localization of the cell wall GPI-anchored proteins.
在真菌中，许多在维持细胞壁功能和参与致病过程中发挥重要作用的蛋白质通过糖基磷脂酰肌醇（GPI）锚定附着在细胞表面。已知，GPI 锚定蛋白中第二甘露糖残基上磷酸乙醇胺（EtN-P）的修饰和去除对于酵母和哺乳动物细胞中 GPI 锚定蛋白的成熟和分拣很重要，但这是一些原生动物寄生虫所缺少的步骤。在烟曲霉（一种机会性真菌病原体，可导致人类侵袭性曲霉病）中，已知 GPI 锚定蛋白参与细胞壁合成和毒力。在本报告中，研究了编码烟曲霉 EtN-P 转移酶 GPI7 的基因。通过删除 gpi7 基因，我们评估了 EtN-P 修饰对烟曲霉形态发生和 GPI 蛋白定位的影响。结果表明，gpi7 基因缺失导致细胞膜 GPI 锚定蛋白减少、细胞壁 GPI 锚定蛋白 Mp1 定位错误、极性异常和自噬。结果表明，GPI 锚上第二甘露糖上 EtN-P 的添加对于细胞壁 GPI 锚定蛋白的运输和定位是必不可少的。
