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

doi:10.1073/pnas.1423456112

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

Molecular Pharmacology

Research output: Contribution to journal › Article › peer-review

49 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 language	English (US)
Pages (from-to)	4636-4641
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	112
Issue number	15
DOIs	https://doi.org/10.1073/pnas.1423456112
State	Published - Apr 14 2015

Keywords

Cell-free membrane fusion
Legionella pneumophila
Lysosome
Phagosome
Phosphoinositides

ASJC Scopus subject areas

General

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10.1073/pnas.1423456112

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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

Jeschke, A, Zehethofer, N, Lindner, B, Krupp, J, Schwudke, D, Haneburger, I, Jovic, M, Backer, JM, 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, vol. 112, no. 15, pp. 4636-4641. https://doi.org/10.1073/pnas.1423456112

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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.",

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AU - Jeschke, Andreas

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AU - Lindner, Buko

AU - Krupp, Jessica

AU - Schwudke, Dominik

AU - Haneburger, Ina

AU - Jovic, Marko

AU - Backer, Jonathan M.

AU - Balla, Tamas

AU - Hilbi, Hubert

AU - Haas, Albert

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N2 - 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.

AB - 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.

KW - Cell-free membrane fusion

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KW - Phagosome

KW - Phosphoinositides

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

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