IpaC of Shigella binds to the C-terminal domain of beta-catenin.
IpaC of Shigella is essential for initial bacterial entry into epithelial cells. We report here that IpaC interacts with beta-catenin and destabilizes the cadherin-mediated cell adhesion complex. Using a yeast two-hybrid system, we identified beta-catenin as a binding partner of IpaC within the host cell after cell entry, but not in the initial entry. Co-immunoprecipitation, confocal microscopy, and GST pull-down experiments confirmed the intracellular and cell-free interactions between these two proteins. The interaction sites were mapped to the ninth armadillo repeat of beta-catenin and to the C-terminus of IpaC. IpaC-associated beta-catenin was phosphorylated at tyrosine residues. This phosphorylation led to the destabilization of the functional cadherin-catenin complex, which could be a mechanism whereby the epithelial cell-cell tight adhesion is disrupted. These events may facilitate the further basolateral invasion of bacteria through the disrupted space and/or modulate the cell-to-cell spread of Shigella.
Shaikh
Nurmohammad
N
Department of Bacteriology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Terajima
Jun
J
Watanabe
Haruo
H
D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012763:Shigella flexneri / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D015534:Trans-Activators / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D051176:beta Catenin
D000942:Antigens, Bacterial; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; C092342:IpaC protein, Shigella