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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-18542 |
| Date | 01 January 2009 |
| Creators | Sun, Jingru, Schoborg, Robert V. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
Page generated in 0.002 seconds