Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis.
Professional phagocytic cells ingest microbial intruders by engulfing them into phagosomes, which subsequently mature into microbicidal phagolysosomes. Phagosome maturation requires sequential fusion of the phagosome with early endosomes, late endosomes, and lysosomes. Although various phosphoinositides (PIPs) have been detected on phagosomes, it remained unclear which PIPs actually govern phagosome maturation. Here, we analyzed the involvement of PIPs in fusion of phagosomes with various endocytic compartments and identified phosphatidylinositol 4-phosphate [PI(4)P], phosphatidylinositol 3-phosphate [PI(3)P], and the lipid kinases that generate these PIPs, as mediators of phagosome-lysosome fusion. Phagosome-early endosome fusion required PI(3)P, yet did not depend on PI(4)P. Thus, PI(3)P regulates phagosome maturation at early and late stages, whereas PI(4)P is selectively required late in the pathway.
['Jeschke|Andreas|A|', 'Zehethofer|Nicole|N|', 'Lindner|Buko|B|', 'Krupp|Jessica|J|', 'Schwudke|Dominik|D|', 'Haneburger|Ina|I|', 'Jovic|Marko|M|', 'Backer|Jonathan M|JM|', 'Balla|Tamas|T|', 'Hilbi|Hubert|H|', 'Haas|Albert|A|']
D019870:1-Phosphatidylinositol 4-Kinase D000818:Animals D002460:Cell Line D002474:Cell-Free System D002851:Chromatography, High Pressure Liquid D011992:Endosomes D015151:Immunoblotting D007425:Intracellular Membranes D008247:Lysosomes D008264:Macrophages D013058:Mass Spectrometry D008561:Membrane Fusion D051379:Mice D008856:Microscopy, Fluorescence D008863:Microspheres D010587:Phagocytosis D010588:Phagosomes D019869:Phosphatidylinositol 3-Kinases D018129:Phosphatidylinositol Phosphates
phagosome lysosome phosphoinositides Legionella pneumophila cell-free membrane fusion