title: Yersinia entry into host cells requires Rab5-dependent dephosphorylation of PI(4,5)P₂ and membrane scission.
abstract: Some bacteria invade host cells by triggering a process akin to phagocytosis. We analyzed the mechanisms underlying invasion vacuole formation by the bacterium Yersinia pseudotuberculosis. After engaging integrins on host cells, Yersinia resided in PI(4,5)P₂-rich, membrane-bound compartments called "prevacuoles" that were inaccessible to extracellular antibodies but remained connected to the plasma membrane. The scission of prevacuoles to form separate, sealed compartments coincided with and required PI(4,5)P₂ hydrolysis. At the time of scission, the inositol 5-phosphatases OCRL and Inpp5b were recruited to prevacuoles. This recruitment and subsequent PI(4,5)P₂ hydrolysis required the association of the GTPase Rab5 with prevacuoles. Phosphatidylinositol 3-kinase activity was required for fusion of Rab5-positive vesicles with prevacuoles and scission of nascent vacuoles from the plasma membrane. Thus, Yersinia invasion involves a multistep process in which the bacteria form a protective prevacuole and then recruit host factors to induce membrane fission, allowing the bacteria to invade the cell.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Sarantis
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Balkin
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008954:Models, Biological; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D014617:Vacuoles / Q000382:microbiology; D015011:Yersinia pseudotuberculosis / Q000472:pathogenicity*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D058539:Phosphatidylinositol 3-Kinase; D019269:Phosphatidylinositol 4,5-Diphosphate; D010744:Phosphoric Monoester Hydrolases; D020696:rab5 GTP-Binding Proteins; D000099182:Phosphoinositide 5-Phosphatases; C075695:OCRL protein, human