Journal
MICROBES AND INFECTION
Volume 11, Issue 1, Pages 12-19Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2008.10.001
Keywords
Chlamydia trachomatis; Nectin-1; Adherens junction; CPAF
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Funding
- East Tennessee State University (ETSU) [04-024M]
- James H. Quillen College of Medicine
- Department of Microbiology
- ETSU School of Graduate Studies
- University of Texas Health Science Center at San Antonio
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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-CPAF(wt) 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. (c) 2008 Elsevier Masson SAS. All rights reserved.
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