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PMID: 12775840 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA.

Science (New York, N.Y.) ·Vol. 300 ·No. 5624 ·2003-05-30 ·Pages 1430-4

Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S

Abstract

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.

MeSH Terms
Animals Antigens, Bacterial/genetics,metabolism Bacterial Adhesion Bacterial Proteins/genetics,metabolism Cell Adhesion Molecules/metabolism Cell Line Cell Polarity Cell Size Dogs Epithelial Cells/cytology,metabolism,microbiology,ultrastructure Gastric Mucosa Helicobacter pylori/pathogenicity,physiology Humans Intracellular Signaling Peptides and Proteins Junctional Adhesion Molecules Membrane Proteins/metabolism Phosphoproteins/metabolism Phosphorylation Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatases/metabolism Tight Junctions/microbiology,physiology,ultrastructure Tumor Cells, Cultured Zonula Occludens-1 Protein
Chemicals
Antigens, Bacterial Bacterial Proteins Cell Adhesion Molecules Intracellular Signaling Peptides and Proteins Junctional Adhesion Molecules Membrane Proteins Phosphoproteins TJP1 protein, human Zonula Occludens-1 Protein cagA protein, Helicobacter pylori PTPN11 protein, human Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Amieva Manuel R
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. [email protected]
Vogelmann Roger
Covacci Antonello
Tompkins Lucy S
Nelson W James
Falkow Stanley
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1081919
Email
[email protected]
Published
2003-05-30
Pages
1430-4
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3369828
Subset
IM
Grants
NIGMS NIH HHS · R01 GM035527 · United States
NCI NIH HHS · R01 CA092229 · United States
NIAID NIH HHS · AI38459 · United States
NCI NIH HHS · CA92229 · United States
NIGMS NIH HHS · R01GM35227 · United States
NIDCD NIH HHS · DDC DK56339 · United States
NIDDK NIH HHS · P30 DK056339 · United States
NIAID NIH HHS · R01 AI038459 · United States
Corrections
CommentIn
PMID: 14762802
External Links
PubMed source DOI: 10.1126/science.1081919 PMC Full Text View journal details
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