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- W2032355912 endingPage "1163" @default.
- W2032355912 startingPage "1143" @default.
- W2032355912 abstract "Macrophages eliminate pathogens and cell debris through phagocytosis, a process by which particulate matter is engulfed and sequestered into a phagosome. Nascent phagosomes are innocuous organelles resembling the plasma membrane. However, through a maturation process, phagosomes are quickly remodeled by fusion with endosomes and lysosomes to form the phagolysosome. Phagolysosomes are highly acidic and degradative leading to particle decomposition. Phagosome maturation is intimately dependent on the endosomal pathway, during which diverse cargoes are sorted for recycling to the plasma membrane or for degradation in lysosomes. Not surprisingly, various regulators of the endosomal pathway are also required for phagosome maturation, including phosphatidylinositol-3-phosphate, an early endosomal regulator. However, phosphatidylinositol-3-phosphate can be modified by the lipid kinase PIKfyve into phosphatidylinositol-3,5-bisphosphate, which controls late endosome/lysosome functions. The role of phosphatidylinositol-3,5-bisphosphate in macrophages and phagosome maturation remains basically unexplored. Using Fcγ receptor-mediated phagocytosis as a model, we describe our research showing that inhibition of PIKfyve hindered certain steps of phagosome maturation. In particular, PIKfyve antagonists delayed removal of phosphatidylinositol-3-phosphate and reduced acquisition of LAMP1 and cathepsin D, both common lysosomal proteins. Consistent with this, the degradative capacity of phagosomes was reduced but phagosomes appeared to still acidify. We also showed that trafficking to lysosomes and their degradative capacity was reduced by PIKfyve inhibition. Overall, we provide evidence that PIKfyve, likely through phosphatidylinositol-3,5-bisphosphate synthesis, plays a significant role in endolysosomal and phagosome maturation in macrophages." @default.
- W2032355912 created "2016-06-24" @default.
- W2032355912 creator A5001790036 @default.
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- W2032355912 creator A5029733609 @default.
- W2032355912 creator A5038163808 @default.
- W2032355912 creator A5087458196 @default.
- W2032355912 date "2014-08-16" @default.
- W2032355912 modified "2023-10-16" @default.
- W2032355912 title "PIKfyve Inhibition Interferes with Phagosome and Endosome Maturation in Macrophages" @default.
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- W2032355912 doi "https://doi.org/10.1111/tra.12199" @default.
- W2032355912 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25041080" @default.
- W2032355912 hasPublicationYear "2014" @default.
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