論文 - 詳細
| RRC ID | 18530 |
|---|---|
| 著者 | Nagahama M, Itohayashi Y, Hara H, Higashihara M, Fukatani Y, Takagishi T, Oda M, Kobayashi K, Nakagawa I, Sakurai J. |
| タイトル | Cellular vacuolation induced by Clostridium perfringens epsilon-toxin. |
| ジャーナル | FEBS J |
| Abstract |
The epsilon-toxin of Clostridium perfringens forms a heptamer in the membranes of Madin-Darby canine kidney cells, leading to cell death. Here, we report that it caused the vacuolation of Madin-Darby canine kidney cells. The toxin induced vacuolation in a dose-dependent and time-dependent manner. The monomer of the toxin formed oligomers on lipid rafts in membranes of the cells. Methyl-β-cyclodextrin and poly(ethylene glycol) 4000 inhibited the vacuolation. Epsilon-toxin was internalized into the cells. Confocal microscopy revealed that the internalized toxin was transported from early endosomes (early endosome antigen 1 staining) to late endosomes and lysosomes (lysosomal-associated membrane protein 2 staining) and then distributed to the membranes of vacuoles. Furthermore, the vacuolation was inhibited by bafilomycin A1, a V-type ATPase inhibitor, and colchicine and nocodazole, microtubule-depolymerizing agents. The early endosomal marker green fluorescent protein-Rab5 and early endosome antigen 1 did not localize to vacuolar membranes. In contrast, the vacuolar membranes were specifically stained by the late endosomal and lysosomal marker green fluorescent protein-Rab7 and lysosomal-associated membrane protein 2. The vacuoles in the toxin-treated cells were stained with LysoTracker Red DND-99, a marker for late endosomes and lysosomes. A dominant negative mutant of Rab7 prevented the vacuolization, whereas a mutant form of Rab5 was less effective. These results demonstrate, for the first time, that: (a) oligomers of epsilon-toxin formed in lipid rafts are endocytosed; and (b) the vacuoles originating from late endosomes and lysosomes are formed by an oligomer of epsilon-toxin. |
| 巻・号 | 278(18) |
| ページ | 3395-407 |
| 公開日 | 2011-9-1 |
| DOI | 10.1111/j.1742-4658.2011.08263.x |
| PMID | 21781280 |
| MeSH | Animals Bacterial Toxins / antagonists & inhibitors Bacterial Toxins / toxicity* Biomarkers / metabolism Cell Line Dogs Endocytosis / drug effects Endosomes / drug effects Endosomes / metabolism Endosomes / ultrastructure Kidney / drug effects* Kidney / metabolism Kidney / ultrastructure* Kinetics Lysosomal-Associated Membrane Protein 2 / metabolism Lysosomes / drug effects Lysosomes / metabolism Lysosomes / ultrastructure Membrane Microdomains / drug effects Membrane Microdomains / ultrastructure Microtubules / drug effects Mutant Proteins / genetics Mutant Proteins / metabolism Polyethylene Glycols / pharmacology Tubulin Modulators / pharmacology Vacuoles / drug effects* Vacuoles / metabolism Vacuoles / ultrastructure* Vesicular Transport Proteins / metabolism beta-Cyclodextrins / pharmacology rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism rab7 GTP-Binding Proteins |
| IF | 4.392 |
| 引用数 | 24 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MDCK(RCB0995) |