Abstract
The 1-phosphatidylinositol-3-phosphate 5-kinase PIKfyve generates PtdIns3,5P2 on late phagolysosomes, which by recruiting the scission protein Atg18, results in their fragmentation in the normal course of endosome processing. Loss of PIKfyve function causes cellular hypervacuolization in eukaryotes and organ failure in humans. We identified pikfyve as the defective gene in a Dictyostelium mutant that failed to form spores. The amoebas normally differentiated into prespore cells and initiated spore coat protein synthesis in Golgi-derived prespore vesicles. However, instead of exocytosing, the prespore vesicles fused into the single vacuole that typifies the stalk and basal disc cells that support the spores. This process was accompanied by stalk wall biosynthesis, loss of spore gene expression and overexpression of ecmB, a basal disc and stalk-specific gene, but not of the stalk-specific genes DDB_G0278745 and DDB_G0277757. Transdifferentiation of prespore into stalk-like cells was previously observed in mutants that lack early autophagy genes, like atg5, atg7, and atg9. However, while autophagy mutants specifically lacked cAMP induction of prespore gene expression, pikfyve− showed normal early autophagy and prespore induction, but increased in vitro induction of ecmB. Combined, the data suggest that the Dictyostelium endosomal system influences cell fate by acting on cell type specific gene expression.
Highlights
Differential phosphorylation of the inositol moiety of phosphatidylinositol (PtdIns) membrane lipids regulates a broad range of cellular processes
PIKfyve Regulates Cell Fate in Dictyostelium acts in a complex with the scaffolding protein Vac14, the PtdIns 5-phosphatase Fig4, the autophagy protein Atg18 and the transmembrane protein Vac7 (McCartney et al, 2014)
We identified pikfyve as the defective gene in a Dictyostelium discoideum mutant with defective spore formation
Summary
Differential phosphorylation of the inositol moiety of phosphatidylinositol (PtdIns) membrane lipids regulates a broad range of cellular processes. PIP3K5 (1-phosphatidylinositol-3-phosphate 5-kinase), known as PIKfyve or Fab, phosphorylates PtdIns3P on the inositol-5 position, and was first recognized as a major regulator of vacuole size in yeast, where Fab is activated by hyperosmotic stress (Gary et al, 1998). PIKfyve Regulates Cell Fate in Dictyostelium acts in a complex with the scaffolding protein Vac, the PtdIns 5-phosphatase Fig, the autophagy protein Atg and the transmembrane protein Vac (McCartney et al, 2014). The complex of Fab, Fig, and Vac proteins localizes to the vacuole, while the mammalian orthologs localize to endosomes and lysosomes. This recruitment is achieved by binding of the FYVE domain of Fab1/PIKfyve to PtdIns3P in the membranes of these organelles. Its interaction with PtdIns3,5P2, generated by PIKfyve activity, causes the multimerization of Atg and activation of its membrane scission activity, which fragments vacuoles into smaller vesicles as part of their normal processing (Gopaldass et al, 2017)
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