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Specific binding of C lostridium perfringens enterotoxin fragment to Claudin‐b and modulation of zebrafish epidermal barrier
Author(s) -
Zhang Jingjing,
Ni Chen,
Yang Zhenguo,
Piontek Anna,
Chen Huapu,
Wang Sijie,
Fan Yiming,
Qin Zhihai,
Piontek Joerg
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12728
Subject(s) - claudin , paracellular transport , clostridium perfringens , enterotoxin , tight junction , zebrafish , biology , microbiology and biotechnology , in vivo , chemistry , biochemistry , permeability (electromagnetism) , escherichia coli , genetics , membrane , bacteria , gene
Claudins (Cldn) are the major components of tight junctions (TJs) sealing the paracellular cleft in tissue barriers of various organs. Zebrafish Cldnb, the homolog of mammalian Cldn4, is expressed at epithelial cell–cell contacts and is important for regulating epidermal permeability. The bacterial toxin Clostridium perfringens enterotoxin ( CPE ) has been shown to bind to a subset of mammalian Cldns. In this study, we used the Cldn‐binding C‐terminal domain of CPE (194–319 amino acids, c CPE 194–319 ) to investigate its functional role in modulating zebrafish larval epidermal barriers. In vitro analyses show that c CPE 194–319 removed Cldn4 from epithelial cells and disrupted the monolayer tightness, which could be rescued by the removal of c CPE 194–319 . Incubation of zebrafish larvae with c CPE 194–319 removed Cldnb specifically from the epidermal cell membrane. Dye diffusion analysis with 4‐kDa fluorescent dextran indicated that the permeability of the epidermal barrier increased due to c CPE 194–319 incubation. Electron microscopic investigation revealed reversible loss of TJ integrity by Cldnb removal. Collectively, these results suggest that c CPE 194–319 could be used as a Cldnb modulator to transiently open the epidermal barrier in zebrafish. In addition, zebrafish might be used as an in vivo system to investigate the capability of c CPE to enhance drug delivery across tissue barriers.