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

Andreas Jeschke, Nicole Zehethofer, Buko Lindner, Jessica Krupp, Dominik Schwudke, Ina Haneburger, Marko Jovic, Jonathan M. Backer, Tamas Balla, Hubert Hilbi, Albert Haas

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26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4636-4641
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number15
DOIs
StatePublished - Apr 14 2015

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Keywords

  • Cell-free membrane fusion
  • Legionella pneumophila
  • Lysosome
  • Phagosome
  • Phosphoinositides

ASJC Scopus subject areas

  • General

Cite this

Jeschke, A., Zehethofer, N., Lindner, B., Krupp, J., Schwudke, D., Haneburger, I., Jovic, M., Backer, J. M., Balla, T., Hilbi, H., & Haas, A. (2015). Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis. Proceedings of the National Academy of Sciences of the United States of America, 112(15), 4636-4641. https://doi.org/10.1073/pnas.1423456112