Cholera toxin (choleragen) is an enterotoxogenic protein complex consisting of a single A subunit (cholera toxin A subunit (CTA)) and a pentamer of B subunits (cholera toxin B subunit (CTB)). It enters the host cell by binding to ganglioside GM1 on the plasma membrane and retrograde into the endoplasmic reticulum via the trans-Golgi network[1-3].
Cholera toxin(0.5ug/ml;3h) treatment of Jurkat cells for 3 h caused a nearly total disappearence of the TcR complex from teh surface of the cell[4,5]. Cholera toxin enters host intestinal epithelia cells, and its retrograde transport to the cytosol results in the massive loss of fluids and electrolytes associated with severe dehydration[6]. Cholera toxin activates adenylate cyclase by catalyzing ADP-ribosylation of Gs alpha, the stimulatory guanine nucleotide-binding protein[7].
References:
[1]. van Heyningen S. Cholera toxin. Biol Rev Camb Philos Soc. 1977 Nov;52(4):509. doi: 10.1111/j.1469-185x.1977.tb00858.x. PMID: 203347.
[2]. Wernick NL, Chinnapen DJ, et,al. Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum. Toxins (Basel). 2010 Mar;2(3):310-25. doi: 10.3390/toxins2030310. Epub 2010 Mar 5. PMID: 22069586; PMCID: PMC3153193.
[3]. Kellner A, Taylor M, et,al. A binding motif for Hsp90 in the A chains of ADP-ribosylating toxins that move from the endoplasmic reticulum to the cytosol. Cell Microbiol. 2019 Oct;21(10):e13074. doi: 10.1111/cmi.13074. Epub 2019 Jul 5. PMID: 31231933; PMCID: PMC6744307.
[4]. Sommermeyer H, Schwinzer R,et,al. Cholera toxin modulates the T cell antigen receptor/CD3 complex but not the CD2 molecule and inhibits signaling via both receptor structures in the human T cell lymphoma Jurkat. Eur J Immunol. 1989 Dec;19(12):2387-90. doi: 10.1002/eji.1830191232. PMID: 2575034.
[5]. Nunes J, Bagnasco M, et,al. Cholera toxin inhibits the increase in cytoplasmic free calcium induced via the CD2 pathway of human T-lymphocyte activation. J Cell Biochem. 1989 Apr;39(4):391-400. doi: 10.1002/jcb.240390405. PMID: 2542344.
[6]. Wands AM, Cervin J, et,al. Fucosylated Molecules Competitively Interfere with Cholera Toxin Binding to Host Cells. ACS Infect Dis. 2018 May 11;4(5):758-770. doi: 10.1021/acsinfecdis.7b00085. Epub 2018 Feb 22. PMID: 29411974; PMCID: PMC5948155.
[7]. Tsai SC, Noda M, et,al. Stimulation of choleragen enzymatic activities by GTP and two soluble proteins purified from bovine brain. J Biol Chem. 1988 Feb 5;263(4):1768-72. PMID: 3123477.
霍乱毒素（霍乱原）是一种肠毒素蛋白复合物,由单个 A 亚基（霍乱毒素 A 亚基 (CTA)）和 B 亚基五聚体（霍乱毒素 B 亚基 (CTB)）组成。它通过与质膜上的神经节苷脂 GM1 结合进入宿主细胞,并通过跨高尔基体网络逆行进入内质网[1-3]。
霍乱毒素(0.5ug/ml;3h)处理处理 Jurkat 细胞 3 小时导致细胞表面的 TcR 复合物几乎完全消失 [4,5]。霍乱毒素进入宿主肠上皮细胞,其逆行转运至胞质溶胶导致与严重脱水相关的大量液体和电解质流失[6]。霍乱毒素通过催化鸟嘌呤核苷酸结合蛋白 Gs α 的 ADP-核糖基化激活腺苷酸环化酶[7]。