The Host Adherens Junction Molecule Nectin-1 Is Degraded by Chlamydial Protease-Like Activity Factor (CPAF) in Chlamydia Trachomatis-Infected Genital Epithelial Cells
Document Type
Article
Publication Date
1-1-2009
Description
Nectin-1 is an adhesion protein implicated in the organization of adherens junctions and tight junctions in epithelial cells. Previous studies in our laboratory demonstrated that nectin-1 accumulation was significantly decreased in Chlamydia trachomatis-infected HeLa cells. In the present study, Western blot analyses indicated that nectin-1 down-regulation was C. trachomatis concentration-dependent. The half-life of nectin-1 was also greatly diminished in C. trachomatis-infected cells compared to that observed in mock-infected cells, indicating that nectin-1 was likely down-regulated post-translationally. The chlamydia-secreted protease CPAF is known to degrade several important host proteins; CPAF expression within infected cells correlated with the time-dependent cleavage of nectin-1. Notably, CPAF proteolytic activity is inhibited by lactacystin but not by the proteosome inhibitor MG132. In vivo inhibition experiments demonstrated that nectin-1 down-regulation was blocked by lactacystin exposure. In contrast, MG132 had no effect. Finally, cell-free cleavage assays demonstrated that functional recombinant GST-CPAFwt protein degrades nectin-1. This degradation was blocked by lactacystin, as previously observed in vivo. Collectively, these results indicate that nectin-1 is degraded by CPAF in C. trachomatis-infected cells, a novel strategy that chlamydiae may use to aid their dissemination.
Citation Information
Sun, Jingru; and Schoborg, Robert V.. 2009. The Host Adherens Junction Molecule Nectin-1 Is Degraded by Chlamydial Protease-Like Activity Factor (CPAF) in Chlamydia Trachomatis-Infected Genital Epithelial Cells. Microbes and Infection. Vol.11(1). 12-19. https://doi.org/10.1016/j.micinf.2008.10.001 PMID: 18983929 ISSN: 1286-4579