与LDL受体相关的蛋白质LRP6调解了炭毒素的内部化和致命性
Wensheng Wei1, Quan Lu, G Jilani Chaudry
1Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|March 28, 2006
概括
低密度脂蛋白受体相关蛋白6 (LRP6) 对于炭毒素进入哺乳动物细胞至关重要. 阻断LRP6可以防止毒素内部化,并保护细胞免受致命的影响,从而为炭病对策揭示了一个新的目标.
科学领域:
- 细胞生物学 细胞生物学
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
背景情况:
- 微生物毒素,包括来自Bacillus anthracis的毒素,需要宿主细胞基因功能来产生毒性作用.
- Wnt信号通路使用低密度脂蛋白受体相关蛋白6 (LRP6) 作为核心受体.
研究的目的:
- 研究LRP6在哺乳动物细胞中炭毒素致死性中的作用.
- 确定潜在的新目标,以制定针对炭杆菌毒素的对策.
主要方法:
- 下调LRP6表达和使用主导负的调节.
- 抗体介导的抑制针对LRP6细胞外表图.
- 光显微镜和生物化学分析以研究毒素内部化.
- 研究LRP6,保护性抗原 (PA) 受体 (TEM8/ATR,CMG2) 和炭毒素之间的相互作用.
主要成果:
- 对于哺乳动物细胞中炭毒素致死性,LRP6是必需的.
- 抑制LRP6功能 (通过下调,主导阴性或抗体) 阻断了炭毒素保护抗原 (PA) 的细胞吸收.
- LRP6通过在细胞表面与PA受体 (TEM8/ATR和/或CMG2) 形成复合物来促进毒素内部化,从而使PA结合和进入.
- 这种相互作用揭示了LRP6在毒素进入中以前未知的功能.
结论:
- 低密度脂蛋白受体相关蛋白6 (LRP6) 在介导炭毒素进入宿主细胞方面发挥着关键的,以前未被识别的作用.
- 通过与PA受体相互作用来促进毒素内化,LRP6的功能将其确定为开发新型炭病对策的有希望的治疗标.
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