title: Transcriptome and biochemical analysis reveals that suppression of GPI-anchor synthesis leads to autophagy and possible necroptosis in Aspergillus fumigatus.
abstract: Previously, it has been shown that GPI proteins are required for cell wall synthesis and organization in Aspergillus fumigatus, a human opportunistic pathogen causing life-threatening invasive aspergillosis (IA) in immunocompromised patients. Blocking GPI anchor synthesis leads to severe phenotypes such as cell wall defects, increased cell death, and attenuated virulence. However, the mechanism by which these phenotypes are induced is unclear. To gain insight into global effects of GPI anchoring in A. fumigatus, in this study a conditional expression mutant was constructed and a genome wide transcriptome analysis was carried out. Our results suggested that suppression of GPI anchor synthesis mainly led to activation of phosphatidylinositol (PtdIns) signaling and ER stress. Biochemical and morphological evidence showed that autophagy was induced in response to suppression of the GPI anchor synthesis, and also an increased necroptosis was observed. Based on our results, we propose that activation of PtdIns3K and increased cytosolic Ca(2+), which was induced by both ER stress and PtdIns signaling, acted as the main effectors to induce autophagy and possible necroptosis.
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Yan
authors.forename: Ting
authors.initials: T
authors.lastname: Du
authors.forename: Wan
authors.initials: W
authors.lastname: Zhao
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartmann
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Lü
authors.forename: Haomiao
authors.initials: H
authors.lastname: Ouyang
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D001343:Autophagy / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D023061:Gene Order; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010716:Phosphatidylinositols / Q000378:metabolism; D014176:Protein Biosynthesis; D015398:Signal Transduction
chemical_list: D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D010716:Phosphatidylinositols; C080086:phosphatidylinositol glycan-class A protein; D002118:Calcium