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On the Interaction of Clostridium perfringens Enterotoxin with Claudins
Leibniz-Institut für molekulare Pharmakologie, Robert-Rössle-Str.10, 13125 Berlin, Germany
* Author to whom correspondence should be addressed.
Received: 5 May 2010; in revised form: 21 May 2010 / Accepted: 4 June 2010 / Published: 8 June 2010
Abstract: Clostridium perfringens causes one of the most common foodborne illnesses, which is largely mediated by the Clostridium perfringens enterotoxin (CPE). The toxin consists of two functional domains. The N-terminal region mediates the cytotoxic effect through pore formation in the plasma membrane of the mammalian host cell. The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins. Claudin-3 and claudin-4 have been shown to be receptors for CPE with very high affinity. The toxin binds with weak affinity to claudin-1 and -2 but contribution of these weak binding claudins to CPE-mediated disease is questionable. cCPE is not cytotoxic, however, it is a potent modulator of tight junctions. This review describes recent progress in the molecular characterization of the cCPE-claudin interaction using mutagenesis, in vitro binding assays and permeation studies. The results promote the development of recombinant cCPE-proteins and CPE-based peptidomimetics to modulate tight junctions for improved drug delivery or to treat tumors overexpressing claudins.
Keywords: Claudins; Clostridium perfringens enterotoxin; drug delivery; tight junction
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Veshnyakova, A.; Protze, J.; Rossa, J.; Blasig, I.E.; Krause, G.; Piontek, J. On the Interaction of Clostridium perfringens Enterotoxin with Claudins. Toxins 2010, 2, 1336-1356.
Veshnyakova A, Protze J, Rossa J, Blasig IE, Krause G, Piontek J. On the Interaction of Clostridium perfringens Enterotoxin with Claudins. Toxins. 2010; 2(6):1336-1356.
Veshnyakova, Anna; Protze, Jonas; Rossa, Jan; Blasig, Ingolf E.; Krause, Gerd; Piontek, Joerg. 2010. "On the Interaction of Clostridium perfringens Enterotoxin with Claudins." Toxins 2, no. 6: 1336-1356.