Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes.
Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes.
复制标题
DOI：
10.3390/toxins8030067
复制
发表时间：
2016-03-08
期刊：
影响因子：
4.2
通讯作者：
Fairn GD
中科院分区：
文献类型：
--
作者：
Maekawa M;Yang Y;Fairn GD
胆固醇是真核生物细胞膜的重要结构成分。质膜外表面小叶中的胆固醇被认为与鞘脂和特定蛋白质形成膜纳米结构域。此外，胆固醇存在于内体的细胞内膜中，并在膜运输中具有重要功能。此外，细胞胆固醇稳态和从头合成的调节依赖于通过囊泡和非囊泡途径的转运。因此，可视化和检测细胞内胆固醇的能力，特别是在质膜中，对于理解与胆固醇和纳米结构域相关的复杂生物学至关重要。产气荚膜梭菌溶血素0（PFO）θ毒素是由厌氧细菌产气荚膜梭菌分泌的毒素之一，并且该毒素在质膜中形成孔，引起细胞裂解。众所周知，PFO识别并结合质膜外表面小叶中的胆固醇，PFO的结构域4（D4）足以结合胆固醇。最近的研究已经利用这种高亲和力的胆固醇结合结构域，通过使用无毒的PFO或分离的D4来创建各种胆固醇生物传感器。这篇综述强调了这些PFO衍生的胆固醇生物传感器的特点和有用性，以及与之相关的主要发现。
Cholesterol is an essential structural component of cellular membranes in eukaryotes. Cholesterol in the exofacial leaflet of the plasma membrane is thought to form membrane nanodomains with sphingolipids and specific proteins. Additionally, cholesterol is found in the intracellular membranes of endosomes and has crucial functions in membrane trafficking. Furthermore, cellular cholesterol homeostasis and regulation of de novo synthesis rely on transport via both vesicular and non-vesicular pathways. Thus, the ability to visualize and detect intracellular cholesterol, especially in the plasma membrane, is critical to understanding the complex biology associated with cholesterol and the nanodomains. Perfringolysin O (PFO) theta toxin is one of the toxins secreted by the anaerobic bacteria Clostridium perfringens and this toxin forms pores in the plasma membrane that causes cell lysis. It is well understood that PFO recognizes and binds to cholesterol in the exofacial leaflets of the plasma membrane, and domain 4 of PFO (D4) is sufficient for the binding of cholesterol. Recent studies have taken advantage of this high-affinity cholesterol-binding domain to create a variety of cholesterol biosensors by using a non-toxic PFO or the D4 in isolation. This review highlights the characteristics and usefulness of, and the principal findings related to, these PFO-derived cholesterol biosensors.