RRC ID |
56070
|
Author |
Nagahama M, Takehara M, Miyamoto K, Ishidoh K, Kobayashi K.
|
Title |
Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin.
|
Journal |
Toxins (Basel)
|
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.
|
Volume |
10(5)
|
Published |
2018-5-20
|
DOI |
10.3390/toxins10050209
|
PII |
toxins10050209
|
PMID |
29783772
|
PMC |
PMC5983265
|
MeSH |
ADP Ribose Transferases / pharmacology*
Animals
Bacterial Toxins / pharmacology*
Biological Transport
Dogs
Madin Darby Canine Kidney Cells
Recombinant Proteins / pharmacology
Sphingomyelin Phosphodiesterase / metabolism*
|
IF |
3.895
|
Times Cited |
2
|
Resource |
Human and Animal Cells |
MDCK(RCB0995) |