アントラックス毒素は,Rab11/Sec15エクソシストによる内細胞循環を協力的に阻害する
Annabel Guichard1, Shauna M McGillivray, Beatriz Cruz-Moreno
1Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0349, USA.
Nature
|October 15, 2010
まとめ
炭菌毒素,致死因 (LF) と腫因子 (EF) は,ハエとヒトの細胞の両方のRab11/Sec15エクソシストを破壊する. この障害は,バチルス・アントラシス感染中に血管の漏れとショックを引き起こします.
科学分野:
- 微生物学 微生物学とは
- 細胞生物学 細胞生物学
- 毒理学 毒理学 毒理学
背景:
- バチルス・アントラシスは,血管の漏れとショックによって特徴づけられる致命的な病気である炭菌を引き起こす.
- 炭毒素,致死因 (LF) と腫因子 (EF) は,主要な毒性の要因である.
- 初期の毒素標的は知られているが,後期的なメカニズムは不明である.
研究 の 目的:
- 感染の遅い段階で,炭菌毒素の新しい宿主標的を特定するために.
- 炭病原性におけるRab11/Sec15エクソシストの役割を明らかにする.
- モデル生物とヒト細胞における保存された毒素メカニズムを調査する.
主な方法:
- 毒素標的をスクリーニングするためのモデル生物としてDrosophila melanogasterを使用しました.
- 毒素媒介細胞プロセスにおけるRab11/Sec15エクソシスト複合体の機能を調査した.
- 膀形成,ノッチシグナル伝達,およびハエとヒトの両方の内皮細胞の結合点における毒素の効果を調べた.
主要な成果:
- LFとEFの両方の新しい標的として,内皮循環に関与するRab11/Sec15エクソシストを特定しました.
- EFとLFがRab11/Sec15の機能を協調的に破壊し,膀の形成を阻害することを実証しました.
- この障害がノッチ信号の減少と,人間の細胞に保存される,アデレンス接合点でのDE-カデリンの減少につながることを示した.
結論:
- 炭毒素EFとLFは,内細胞循環の重要な構成要素であるRab11/Sec15エクソシストに収束する.
- アントラックス毒素によるRab11/Sec15エクソシストの破壊は,血管壁の機能障害とショックに寄与する.
- この研究は,種間の炭病原性の保存されたメカニズムを明らかにしています.
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