炭毒素通过Rab11/Sec15外囊合作抑制内细胞循环
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
概括
炭毒素,致命因子 (LF) 和瘤因子 (EF) 破坏了和人类细胞中的Rab11/Sec15外囊. 这种干扰在Bacillus anthracis感染期间导致血管泄漏和冲击.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 炭杆菌 (Bacillus anthracis) 引起炭,这是一种致命的疾病,其特点是血管泄漏和冲击.
- 炭毒素,致命因子 (LF) 和瘤因子 (EF) 是关键的毒性因素.
- 虽然已知最初的毒素点,但后期的机制尚不清楚.
研究的目的:
- 在感染的晚期阶段识别新型的炭毒素宿主目标.
- 阐明Rab11/Sec15外囊在炭病原发生中的作用.
- 在模型生物和人类细胞中研究保存的毒素机制.
主要方法:
- 使用Drosophila melanogaster作为一种模型生物来选毒素标.
- 研究了Rab11/Sec15外囊复合体在毒素介导的细胞过程中的功能.
- 检查了毒素对囊泡形成的影响,Notch信号传递,以及在和人类内皮细胞中的粘附结.
主要成果:
- 确定了参与内细胞循环的Rab11/Sec15外囊,作为LF和EF的新目标.
- 证明EF和LF协调地破坏Rab11/Sec15功能,抑制囊泡的形成.
- 表明这种干扰导致减少了Notch信号传递和减少了DE-cadherin在粘附结处,在人体细胞中保存.
结论:
- 炭毒素EF和LF汇聚在Rab11/Sec15外囊上,这是内细胞循环的关键组成部分.
- 由于炭毒素破坏Rab11/Sec15外囊,导致血管屏障功能障碍和休克.
- 这项研究揭示了跨物种的炭病原发生的保存机制.
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