Burnett School of Biomedical Sciences, 12722 Research Parkway, University of Central Florida, Orlando, FL 32826, USA.
Cell Signal. 2022 Dec;100:110489. doi: 10.1016/j.cellsig.2022.110489. Epub 2022 Oct 8.
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 signaling pathway that stimulates chloride efflux into the gut, with diarrhea resulting from the accompanying osmotic movement of water into the intestinal lumen. G protein signaling is not the only host system manipulated by cholera toxin, however. Other cellular mechanisms and signaling 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 signaling pathways and other cell biology events to elicit a diarrheal response from the host.
霍乱弧菌定植于小肠并将霍乱毒素释放到细胞外空间。毒素结合到上皮细胞的顶端表面，被内吞进入宿主的内体膜系统，并逃入细胞质，在那里通过 ADP-核糖基化激活异三聚体 G 蛋白的刺激α亚基。这启动了 cAMP 依赖性信号通路，刺激氯离子流出肠道，伴随着水进入肠腔的伴随渗透运动导致腹泻。然而，霍乱毒素并非唯一操纵宿主系统的 G 蛋白信号。在中毒过程中活跃的其他细胞机制和信号通路包括通过脂筏内吞作用、逆行运输到内质网、用于将蛋白质递送到细胞质的内质网相关降解系统、未折叠蛋白反应以及通过降解或 ADP-核糖基水解酶的功能使 G 蛋白失活。尽管认为毒素诱导的氯离子外排是不可逆事件，但对这些过程的改变可以促进细胞从中毒中恢复。这篇综述将强调霍乱毒素如何利用信号通路和其他细胞生物学事件引起宿主的腹泻反应。
