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Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis.

  • Jeschke A Cell Biology Institute, University of Bonn, 53121 Bonn, Germany;
  • Zehethofer N Division of Immunochemistry, Department of Molecular Infection Biology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, 23845 Borstel, Germany;
  • Lindner B Division of Immunochemistry, Department of Molecular Infection Biology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, 23845 Borstel, Germany;
  • Krupp J Cell Biology Institute, University of Bonn, 53121 Bonn, Germany;
  • Schwudke D Division of Immunochemistry, Department of Molecular Infection Biology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, 23845 Borstel, Germany;
  • Haneburger I Department of Medicine, Max von Pettenkofer-Institute, Ludwig-Maximilians University Munich, 80336 Munich, Germany; Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland;
  • Jovic M Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and.
  • Backer JM Molecular Pharmacology, Belfer Institute for Advanced Biomedical Sciences, Albert Einstein College of Medicine, Bronx, NY 10461.
  • Balla T Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and.
  • Hilbi H Department of Medicine, Max von Pettenkofer-Institute, Ludwig-Maximilians University Munich, 80336 Munich, Germany; Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland;
  • Haas A Cell Biology Institute, University of Bonn, 53121 Bonn, Germany; albert.haas@uni-bonn.de.
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  • 2015-04-01
Published in:
  • Proceedings of the National Academy of Sciences of the United States of America. - 2015
Legionella pneumophila
cell-free membrane fusion
lysosome
phagosome
phosphoinositides
1-Phosphatidylinositol 4-Kinase
Animals
Cell Line
Cell-Free System
Chromatography, High Pressure Liquid
Endosomes
Immunoblotting
Intracellular Membranes
Lysosomes
Macrophages
Mass Spectrometry
Membrane Fusion
Mice
Microscopy, Fluorescence
Microspheres
Phagocytosis
Phagosomes
Phosphatidylinositol 3-Kinases
Phosphatidylinositol Phosphates
English 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.
Language
  • English
Open access status
bronze
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https://sonar.ch/global/documents/96659
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