Chlamydia trachomatis disrupts N-cadherin-dependent cell-cell junctions and sequesters beta-catenin in human cervical epithelial cells.
The cadherin/catenin complex serves as an important structural component of adherens junctions in epithelial cells. Under certain conditions, beta-catenin can be released from this complex and interact with transcription factors in the nucleus to stimulate the expression of genes that regulate apoptosis and cell cycle control. While studying the effects of the bacterial pathogen Chlamydia trachomatis on human cervical epithelial cells in culture, we observed that C. trachomatis caused the epithelial cells to separate from each other without detaching from their growing surface. The objective of the present study was to determine if this effect might involve the disruption of the cadherin/catenin complex. Primary cultures of human cervical epithelial cells or HeLa cells were infected with C. trachomatis serovar E. Cadherin-like immunoreactive materials and beta-catenin were visualized by immunofluorescence. Preliminary studies showed that N-cadherin was the primary cadherin expressed in both the primary cultures and the HeLa cells. In noninfected cells, N-cadherin and beta-catenin were colocalized at the intercellular junctional complexes. By contrast, the infected cells showed a marked loss of both N-cadherin and beta-catenin labeling from the junctional complexes and the concomitant appearance of intense beta-catenin labeling associated with the chlamydial inclusion. The results of Western blot analyses of extracts of C. trachomatis showed no evidence of cross-reactivity with the beta-catenin antibody. These results indicate that C. trachomatis causes the breakdown of the N-cadherin/beta-catenin complex and that the organism can sequester beta-catenin within the chlamydial inclusion. This could represent an important mechanism by which C. trachomatis alters epithelial cell function.
Prozialeck
Walter C
WC
Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois 60515, USA.
Fay
Michael J
MJ
Lamar
Peter C
PC
Pearson
Celeste A
CA
Sigar
Ira
I
Ramsey
Kyle H
KH
D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism*; D002584:Cervix Uteri / Q000473:pathology*; D002692:Chlamydia trachomatis / Q000472:pathogenicity*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D007365:Intercellular Junctions / Q000473:pathology*; D015534:Trans-Activators; D002583:Uterine Cervical Neoplasms / Q000209:etiology; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin