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

作者：Jeschke Andreas; Zehethofer Nicole; Lindner Buko; Krupp Jessica; Schwudke Dominik; Haneburger Ina; Jovic Marko; Backer Jonathan M; Balla Tamas; Hilbi Hubert; Haas Albert^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(15): 4636-4641.

DOI：10.1073/pnas.1423456112

• phosphoinositides
• cell-free membrane fusion
• phagosome
• lysosome
• Legionella pneumophila

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.

• 出版日期2015-4-14
• 单位河北医科大学