RRC ID 68806
Author Nagahama M, Kobayashi K, Takehara M.
Title Cathepsin Release from Lysosomes Promotes Endocytosis of Clostridium perfringens Iota-Toxin.
Journal Toxins (Basel)
Abstract 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.
Volume 13(10)
Published 2021-10-12
DOI 10.3390/toxins13100721
PII toxins13100721
PMID 34679014
PMC PMC8537257
MeSH ADP Ribose Transferases / pharmacology* Animals Bacterial Toxins / pharmacology* Cathepsin B / metabolism Cathepsin L / metabolism Clostridium perfringens Cysteine Proteinase Inhibitors / metabolism Dogs Endocytosis / drug effects* Lysosomes / metabolism Madin Darby Canine Kidney Cells Sphingomyelin Phosphodiesterase / metabolism*
IF 3.531
Resource
Human and Animal Cells MDCK(RCB0995)