The manipulation of cell signaling and host cell biology by cholera toxin.
The manipulation of cell signaling and host cell biology by cholera toxin.
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DOI：
10.1016/j.cellsig.2022.110489
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发表时间：
2022-12
影响因子：
4.8
通讯作者：
Teter, Ken
中科院分区：
文献类型：
--
作者：
White, Christopher;Bader, Carly;Teter, Ken
霍乱弧菌定植于小肠并将霍乱毒素释放到细胞外空间。该毒素结合到上皮的顶端表面，内化到宿主内膜系统中，并逃逸到胞质溶胶中，在胞质溶胶中通过ADP-核糖基化激活异源三聚体G蛋白的刺激性α亚基。这启动了一个cAMP依赖性信号通路，刺激氯流出到肠道中，腹泻是由伴随的水渗透运动进入肠腔引起的。然而，G蛋白信号并不是霍乱毒素操纵的唯一宿主系统。在中毒过程中活跃的其他细胞机制和信号传导途径包括通过脂筏的内吞作用、逆行转运至内质网、用于蛋白质递送至胞质溶胶的内质网相关降解系统、未折叠的蛋白质反应和通过ADP-核糖基水解酶的降解或功能的G蛋白失活。虽然毒素诱导的氯离子外流被认为是一个不可逆的事件，这些过程的改变可以促进细胞从中毒中恢复。本文将重点介绍霍乱毒素如何利用信号通路和其他细胞生物学事件来引起宿主的腹泻反应。
Vibrio cholerae colonizes the small intestine and releases cholera toxin into the extracellular space. The toxin binds to the apical surface of the epithelium, is internalized into the host endomembrane system, and escapes into the cytosol where it activates the stimulatory alpha subunit of the heterotrimeric G protein by ADP-ribosylation. This initiates a cAMP-dependent signalling pathway that stimulates chloride efflux into the gut, with diarrhea resulting from the accompanying osmotic movement of water into the intestinal lumen. G protein signalling is not the only host system manipulated by cholera toxin, however. Other cellular mechanisms and signalling pathways active in the intoxication process include endocytosis through lipid rafts, retrograde transport to the endoplasmic reticulum, the endoplasmic reticulum-associated degradation system for protein delivery to the cytosol, the unfolded protein response, and G protein de-activation through degradation or the function of ADP-ribosyl hydrolases. Although toxin-induced chloride efflux is thought to be an irreversible event, alterations to these processes could facilitate cellular recovery from intoxication. This review will highlight how cholera toxin exploits signalling pathways and other cell biology events to elicit a diarrheal response from the host.