Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2.

Fennessey CM, Sheng J, Rubin DH, McClain MS
PLoS One. 2012 7 (10): e46866

PMID: 23056496 · PMCID: PMC3462777 · DOI:10.1371/journal.pone.0046866

Evidence from multiple studies suggests that Clostridium perfringens ε-toxin is a pore-forming toxin, assembling into oligomeric complexes in the plasma membrane of sensitive cells. In a previous study, we used gene-trap mutagenesis to identify mammalian factors contributing to toxin activity, including caveolin-2 (CAV2). In this study, we demonstrate the importance of caveolin-2 and its interaction partner, caveolin-1 (CAV1), in ε-toxin-induced cytotoxicity. Using CAV2-specific shRNA in a toxin-sensitive human kidney cell line, ACHN, we confirmed that cells deficient in CAV2 exhibit increased resistance to ε-toxin. Similarly, using CAV1-specific shRNA, we demonstrate that cells deficient in CAV1 also exhibit increased resistance to the toxin. Immunoprecipitation of CAV1 and CAV2 from ε-toxin-treated ACHN cells demonstrated interaction of both CAV1 and -2 with the toxin. Furthermore, blue-native PAGE indicated that the toxin and caveolins were components of a 670 kDa protein complex. Although ε-toxin binding was only slightly perturbed in caveolin-deficient cells, oligomerization of the toxin was dramatically reduced in both CAV1- and CAV2-deficient cells. These results indicate that CAV1 and -2 potentiate ε-toxin induced cytotoxicity by promoting toxin oligomerization - an event which is requisite for pore formation and, by extension, cell death.

MeSH Terms (12)

Animals Bacterial Toxins Caveolin 1 Caveolin 2 Cell Survival Dogs Gene Knockdown Techniques Humans Madin Darby Canine Kidney Cells Protein Multimerization Protein Structure, Quaternary RNA, Small Interfering

Connections (1)

This publication is referenced by other Labnodes entities:

Links