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Lymphostatin regulates epithelial barrier function
Author(s) -
Klapproth JanMichael Axel,
Sasaki Maiko,
Nusrat Asma,
Babbin Brian
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a191-c
Subject(s) - rhoa , cdc42 , tight junction , paracellular transport , microbiology and biotechnology , barrier function , chemistry , rac1 , gtpase , intestinal epithelium , adherens junction , protease , biology , epithelium , biochemistry , signal transduction , enzyme , genetics , cell , cadherin , membrane , permeability (electromagnetism)
Lymphocyte inhibitory factor A ( lifA ) encodes for lymphostatin from Citrobacter rodentium and is responsible for colonization of extra‐intestinal organs. We hypothesize that lymphostatin regulates epithelial barrier function by modifying Rho GTPases. lifA glycosyltransferase (CrGlM21) and the protease motif (CrPrM5) were mutated by homologous recombination and epithelial barrier function was analyzed by FITC‐dextran flux. Rho GTPase activation status was determined by Rhotekin and Pak binding assays. All strains induced increased paracellular flux which was significantly less for CrGlM21. Interestingly, ZO‐1 was redistributed from tight junctions (TJs) following infection with WT and CrPrM5 but not CrGlM21. While both WT and CrPrM5 inhibited activation of Cdc42, infection with CrGlM21 resulted in increased Cdc42 activity. In contrast to WT and CrGlM21, CrPrM5 failed to activate RhoA. In summary, lifA glycosyltransferase motif is critical for inhibition of Cdc42 and the protease motif is essential for activation of RhoA. We conclude that inhibition of Cdc42 by the glycosyltransferase plays a significant role in regulating epithelial barrier function.