Toxins 2018, 10(5), 209; https://doi.org/10.3390/toxins10050209
Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin
1
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
2
Division of Molecular Biology, Institute for Health Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
*
Author to whom correspondence should be addressed.
Received: 21 April 2018 / Revised: 14 May 2018 / Accepted: 18 May 2018 / Published: 20 May 2018
(This article belongs to the Special Issue Bacterial Pore-Forming Toxins)
Abstract
Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca2+. Ib induced the extracellular release of ASMase in the presence of Ca2+. ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells. View Full-Text
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Nagahama, M.; Takehara, M.; Miyamoto, K.; Ishidoh, K.; Kobayashi, K. Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin. Toxins 2018, 10, 209.
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