title: Neisseria gonorrhoeae porin P1.B induces endosome exocytosis and a redistribution of Lamp1 to the plasma membrane.
abstract: The immunoglobulin A (IgA) protease secreted by pathogenic Neisseria spp. cleaves Lamp1, thereby altering lysosomes in a cell and promoting bacterial intracellular survival. We sought to determine how the IgA protease gains access to cellular Lamp1 in order to better understand the role of this cleavage event in bacterial infection. In a previous report, we demonstrated that the pilus-induced Ca(2+) transient triggers lysosome exocytosis in human epithelial cells. This, in turn, increases the level of Lamp1 at the plasma membrane, where it can be cleaved by IgA protease. Here, we show that porin also induces a Ca(2+) flux in epithelial cells. This transient is similar in nature to that observed in phagocytes exposed to porin. In contrast to the pilus-induced Ca(2+) transient, the porin-induced event does not trigger lysosome exocytosis. Instead, it stimulates exocytosis of early and late endosomes and increases Lamp1 on the cell surface. These results indicate that Neisseria pili and porin perturb Lamp1 trafficking in epithelial cells by triggering separate and distinct Ca(2+)-dependent exocytic events, bringing Lamp1 to the cell surface, where it can be cleaved by IgA protease.
authors.affiliation: Department of Molecular Microbiology and Immunology, L220, Oregon Health and Science University, Portland, Oregon 97201, USA. ayalap@ohsu.edu
authors.forename: Patricia
authors.initials: P
authors.lastname: Ayala
authors.forename: Brandi
authors.initials: B
authors.lastname: Vasquez
authors.forename: Lee
authors.initials: L
authors.lastname: Wetzler
authors.forename: Magdalene
authors.initials: M
authors.lastname: So
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects*; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D009344:Neisseria gonorrhoeae / Q000502:physiology*; D018272:Porins / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D052118:Lysosomal-Associated Membrane Protein 1; D051907:Lysosomal Membrane Proteins; D018272:Porins; C057699:porin protein, Neisseria; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase; D002118:Calcium