RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin.

RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin.
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DOI:
10.1016/j.chom.2011.01.005
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发表时间:
2011-02-17
影响因子:
30.3
通讯作者:
Aroian RV
Aroian RV
中科院分区:
医学1区
文献类型:
--
作者:
Los FC;Kao CY;Smitham J;McDonald KL;Ha C;Peixoto CA;Aroian RV

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致病菌分泌的成孔毒素是最常见的细菌蛋白毒素,是感染的重要毒力因子。pft在宿主细胞膜上打洞,尽管细胞可以抵消由此造成的膜损伤,但其潜在机制尚不清楚。以秀丽隐杆线虫为模型,我们在体内和完整的上皮中证明,肠道细胞对pft的反应是通过增加内吞作用水平来实现的,这取决于rabb -5和rabb -11,它们是内吞和胞吐事件的主要调节因子。此外,我们发现rabb -5和rabb -11是防止PFT和恢复质膜完整性所必需的。其中一个物理机制是肠上皮细胞顶侧的微绒毛依赖rab -11排出。因此,通过改变质膜动力学,特定的囊泡运输途径保护细胞免受pft对质膜完整性的攻击。
Pore-forming toxins (PFTs) secreted by pathogenic bacteria are the most common bacterial protein toxins and are important virulence factors for infection. PFTs punch holes in host cell plasma membranes and although cells can counteract the resulting membrane damage, the underlying mechanisms at play remain unclear. Using Caenorhabditis elegans as a model, we demonstrate in vivo and in an intact epithelium that intestinal cells respond to PFTs by increasing levels of endocytosis, dependent upon RAB-5 and RAB-11, which are master regulators of endocytic and exocytic events. Furthermore, we find that RAB-5 and RAB-11 are required for protection against PFT, and to restore integrity to the plasma membrane. One physical mechanism involved is the RAB-11-dependent expulsion of microvilli from the apical side of the intestinal epithelial cells. Specific vesicle-trafficking pathways thus protect cells against an attack by PFTs on plasma membrane integrity, via altered plasma membrane dynamics.
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