title: Neisseria gonorrhoeae breaches the apical junction of polarized epithelial cells for transmigration by activating EGFR.
abstract: Neisseria gonorrhoeae initiates infection at the apical surface of columnar endocervical epithelial cells in the female reproductive tract. These cells provide a physical barrier against pathogens by forming continuous apical junctional complexes between neighbouring cells. This study examines the interaction of gonococci (GC) with polarized epithelial cells. We show that viable GC preferentially localize at the apical side of the cell-cell junction in polarized endometrial and colonic epithelial cells, HEC-1-B and T84. In GC-infected cells, continuous apical junctional complexes are disrupted, and the junction-associated protein β-catenin is redistributed from the apical junction to the cytoplasm and to GC adherent sites; however, overall cellular levels remain unchanged. This redistribution of junctional proteins is associated with a decrease in the 'fence' function of the apical junction but not its 'gate' function. Disruption of the apical junction by removing calcium increases GC transmigration across the epithelial monolayer. GC inoculation induces the phosphorylation of both epidermal growth factor receptor (EGFR) and β-catenin, while inhibition of EGFR kinase activity significantly reduces both GC-induced β-catenin redistribution and GC transmigration. Therefore, the gonococcus is capable of weakening the apical junction and polarity of epithelial cells by activating EGFR, which facilitates GC transmigration across the epithelium.
authors.affiliation: Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Vonetta L
authors.initials: VL
authors.lastname: Edwards
authors.forename: Liang-Chun
authors.initials: LC
authors.lastname: Wang
authors.forename: Valerie
authors.initials: V
authors.lastname: Dawson
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Stein
authors.forename: Wenxia
authors.initials: W
authors.lastname: Song
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D006801:Humans; D007365:Intercellular Junctions / Q000382:microbiology* / Q000502:physiology; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity / Q000502:physiology*; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin; C512478:EGFR protein, human; D066246:ErbB Receptors; D002118:Calcium