In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin
In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin
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DOI：
10.1093/emboj/19.20.5315
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发表时间：
2000-10-16
期刊：
影响因子：
11.4
通讯作者：
Mekalanos, JJ
中科院分区：
文献类型：
--
作者：
Fullner, KJ;Mekalanos, JJ
肠道病原体通常输出毒素，其引起腹泻作为疾病病因的一部分，包括影响细胞骨架结构的毒素。最近，我们发现肠道病原体霍乱弧菌使上皮细胞变圆，这依赖于我们指定为rtxA的基因。在这里，我们研究rtxA与细胞变圆效应的关联，我们发现霍乱弧菌向培养上清液输出大毒素，RTX（毒素重复）毒素，并且该毒素负责细胞变圆。此外，我们发现细胞变圆不是由于坏死，这表明RTX毒素不是孔形成毒素的RTX家族的典型成员，而是RTX毒素导致肌动蛋白应力纤维解聚和细胞肌动蛋白共价交联成二聚体、三聚体和更高的多聚体。这种RTX毒素特异性交联发生在先前用细胞松弛素D圆化的细胞中，表明G-肌动蛋白是毒素靶点。虽然有几种模型解释了我们的观察结果，但我们同时检测到肌动蛋白交联和解聚，这表明RTX毒素具有一种新的作用机制，将其与所有其他已知毒素区分开来。
Enteric pathogens often export toxins that elicit diarrhea as a part of the etiology of disease, including toxins that affect cytoskeletal structure, Recently, we discovered that the intestinal pathogen Vibrio cholerae elicits rounding of epithelial cells that is dependent upon a gene we designated rtxA. Here we investigate the association of rtxA with the cell-rounding effect, We find that V.cholerae exports a large toxin, RTX (repeats-in-toxin) toxin, to culture supernatant fluids and that this toxin is responsible for cell rounding. Furthermore, we find that cell rounding is not due to necrosis, suggesting that RTX toxin is not a typical member of the RTX family of pore-forming toxins, Rather, RTX toxin causes depolymerization of actin stress fibers and covalent cross-linking of cellular actin into dimers, trimers and higher multimers. This RTX toxin-specific cross-linking occurs in cells previously rounded with cytochalasin D, indicating that G-actin is the toxin target. Although several models explain our observations, our simultaneous detection of actin cross-linking and depolymerization points toward a novel mechanism of action for RTX toxin, distinguishing it from all other known toxins.