title: Intracellular periodontal pathogen exploits recycling pathway to exit from infected cells.
abstract: Although human gingival epithelium prevents intrusions by periodontal bacteria, Porphyromonas gingivalis, the most well-known periodontal pathogen, is able to invade gingival epithelial cells and pass through the epithelial barrier into deeper tissues. We previously reported that intracellular P. gingivalis exits from gingival epithelial cells via a recycling pathway. However, the underlying molecular process remains unknown. In the present study, we found that the pathogen localized in early endosomes recruits VAMP2 and Rab4A. VAMP2 was found to be specifically localized in early endosomes, although its localization remained unclear in mammalian cells. A single transmembrane domain of VAMP2 was found to be necessary and sufficient for localizing in early endosomes containing P. gingivalis in gingival epithelial cells. VAMP2 forms a complex with EXOC2/Sec5 and EXOC3/Sec6, whereas Rab4A mediates dissociation of the EXOC complex followed by recruitment of RUFY1/Rabip4, Rab4A effector, and Rab14. Depletion of VAMP2 or Rab4A resulted in accumulation of bacteria in early endosomes and disturbed bacterial exit from infected cells. It is suggested that these novel dynamics allow P. gingivalis to exploit fast recycling pathways promoting further bacterial penetration of gingival tissues.
authors.affiliation: Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita-Osaka, 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita-Osaka, 565-0871, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takada
authors.affiliation: Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita-Osaka, 565-0871, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Kuboniwa
authors.affiliation: Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Suita-Osaka, 565-0871, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Amano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D016866:Bacteroidaceae Infections / Q000378:metabolism / Q000382:microbiology; D001692:Biological Transport; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005881:Gingiva / Q000378:metabolism / Q000382:microbiology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D000072417:Protein Domains; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490685:EXOC3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C465344:RUFY1 protein, human; C494807:VAMP2 protein, human; D050988:Vesicle-Associated Membrane Protein 2; D033921:Vesicular Transport Proteins; C553411:Rab14 protein, human; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins
keywords: Porphyromonas gingivalis; Rab proteins; host-parasite interaction; marginal periodontitis; recycling pathway