Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA.
Helicobacter pylori translocates the protein CagA into gastric epithelial cells and has been linked to peptic ulcer disease and gastric carcinoma. We show that injected CagA associates with the epithelial tight-junction scaffolding protein ZO-1 and the transmembrane protein junctional adhesion molecule, causing an ectopic assembly of tight-junction components at sites of bacterial attachment, and altering the composition and function of the apical-junctional complex. Long-term CagA delivery to polarized epithelia caused a disruption of the epithelial barrier function and dysplastic alterations in epithelial cell morphology. CagA appears to target H. pylori to host cell intercellular junctions and to disrupt junction-mediated functions.
Amieva
Manuel R
MR
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. amieva@stanford.edu
Vogelmann
Roger
R
Covacci
Antonello
A
Tompkins
Lucy S
LS
Nelson
W James
WJ
Falkow
Stanley
S
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D048429:Cell Size; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D005753:Gastric Mucosa; D016480:Helicobacter pylori / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D019108:Tight Junctions / Q000382:microbiology* / Q000502:physiology / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured; D062826:Zonula Occludens-1 Protein
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C080866:cagA protein, Helicobacter pylori; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases