title: Type II phosphatidylinositol 4-kinases promote Listeria monocytogenes entry into target cells.
abstract: Interaction of the Listeria surface protein InlB with the hepatocyte growth factor receptor Met activates signalling events that trigger bacterial internalization into mammalian epithelial cells. We show here that purified phagosomes containing InlB-coated beads display type II phosphatidylinositol 4-kinase (PI4K) activity. In human epithelial HeLa cells, both PI4KIIalpha and PI4KIIbeta isoforms are corecruited with Met around InlB-coated beads or wild-type Listeria during the early steps of internalization, and phosphatidylinositol 4-phosphate [PI(4)P] is detected at the entry site. We demonstrate that PI4KIIalpha or PI4KIIbeta knockdown, but not type III PI4Kbeta knockdown, inhibits Listeria internalization. Production of PI(4)P derivatives such as phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P(3)] upon InlB stimulation is not affected by PI4KIIalpha or beta knockdown, suggesting that these phosphoinositides are generated by a type III PI4K. Strikingly, knockdown of the PI(4)P ligand and clathrin adaptor AP-1 strongly inhibits bacterial entry. Together, our results reveal a yet non-described role for type II PI4Ks in phagocytosis.
authors.affiliation: Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris F-75015, France. pizarroj@pasteur.fr
authors.forename: Javier
authors.initials: J
authors.lastname: Pizarro-Cerdá
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Esteban
authors.initials: E
authors.lastname: Veiga
authors.forename: Helen L
authors.initials: HL
authors.lastname: Yin
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008089:Listeria monocytogenes / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D010716:Phosphatidylinositols / Q000096:biosynthesis; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D018808:Transcription Factor AP-1; C095768:inlB protein, Listeria monocytogenes; C118303:phosphoinositide-3,4,5-triphosphate; D019870:1-Phosphatidylinositol 4-Kinase