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Cathepsin Release from Lysosomes Promotes Endocytosis of Clostridium perfringens Iota-Toxin.
Nagahama, Masahiro; Kobayashi, Keiko; Takehara, Masaya.
Afiliación
  • Nagahama M; Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Yamashiro, Japan.
  • Kobayashi K; Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Yamashiro, Japan.
  • Takehara M; Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Yamashiro, Japan.
Toxins (Basel) ; 13(10)2021 10 12.
Article en En | MEDLINE | ID: mdl-34679014
Iota-toxin from Clostridium perfringens type E is a binary toxin composed of two independent proteins: actin-ADP-ribosylating enzyme component, iota-a (Ia), and binding component, iota-b (Ib). Ib binds to target cell receptors and mediates the internalization of Ia into the cytoplasm. Extracellular lysosomal enzyme acid sphingomyelinase (ASMase) was previously shown to facilitate the internalization of iota-toxin. In this study, we investigated how lysosomal cathepsin promotes the internalization of iota-toxin into target cells. Cysteine protease inhibitor E64 prevented the cytotoxicity caused by iota-toxin, but aspartate protease inhibitor pepstatin-A and serine protease inhibitor AEBSF did not. Knockdown of lysosomal cysteine protease cathepsins B and L decreased the toxin-induced cytotoxicity. E64 suppressed the Ib-induced ASMase activity in extracellular fluid, showing that the proteases play a role in ASMase activation. These results indicate that cathepsin B and L facilitate entry of iota-toxin via activation of ASMase.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingomielina Fosfodiesterasa / Toxinas Bacterianas / ADP Ribosa Transferasas / Endocitosis Límite: Animals Idioma: En Revista: Toxins (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingomielina Fosfodiesterasa / Toxinas Bacterianas / ADP Ribosa Transferasas / Endocitosis Límite: Animals Idioma: En Revista: Toxins (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza