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. 1973 Aug;8(2):208–214. doi: 10.1128/iai.8.2.208-214.1973

Tissue Receptor for Cholera Exotoxin: Postulated Structure from Studies with GM1 Ganglioside and Related Glycolipids

J Holmgren 1, I Lönnroth 1, L Svennerholm 1
PMCID: PMC422834  PMID: 4125267

Abstract

By a double-diffusion precipitation-in-gel technique, isolated cholera toxin as well as its natural toxoid were shown to be fixed and precipitated by the ganglioside GM1 but not by any of the related glycolipids GM3, GM2, GM1-GlcNAc, GD1a, GD1b, GT1, globoside, GA1, and tetrahexoside-GlcNAc. Twenty-five nanograms of GM1 was enough to give a precipitation line with 1.2 μg of toxin, whereas about 50 ng was required with this amount of toxoid. GM1 also inactivated the toxin in the ileal loop as well as in the intradermal models in rabbits. A 1: 1 molar ratio of ganglioside to toxin was found limiting, e.g., 100 pg of GM1 could inactivate 5 ng (about 50 blueing doses) of isolated toxin. GM1 inactivated crude toxin (culture fil rate) with the same efficiency as isolated toxin, and the inactivating capacity of GM1 was unaffected by mixing with other gangliosides, indicating the specificity in the reaction between GM1 and toxin. The other glycolipids tested did not inactivate toxin except GD1a and GA1 which did so with approximately 1,000 times less efficiency than GM1. This identified the portion Gal → GalNAc [Formula: see text] as the critical region in GM1 for toxin fixation, and it is postulated that this may be the tissue receptor structure for the cholera toxin.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Craig J. P. A permeability factor (toxin) found in cholera stools and culture filtrates and its neutralization by convalescent cholera sera. Nature. 1965 Aug 7;207(997):614–616. doi: 10.1038/207614a0. [DOI] [PubMed] [Google Scholar]
  2. HAKOMORI S. A RAPID PERMETHYLATION OF GLYCOLIPID, AND POLYSACCHARIDE CATALYZED BY METHYLSULFINYL CARBANION IN DIMETHYL SULFOXIDE. J Biochem. 1964 Feb;55:205–208. [PubMed] [Google Scholar]
  3. Hakomori S. I., Siddiqui B., Li Y. T., Li S. C., Hellerqvist C. G. Anomeric structure of globoside and ceramide grihexoside of human erythrocytes and hamster fibroblasts. J Biol Chem. 1971 Apr 10;246(7):2271–2277. [PubMed] [Google Scholar]
  4. Holmgren J., Andersson A., Wallerstrom G., Ouchterlony O. Experimental studies on cholera immunization. II. Evidence for protective antitoxic immunity mediated by serum antibodies as well as local antibodies. Infect Immun. 1972 May;5(5):662–667. doi: 10.1128/iai.5.5.662-667.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Laurell C. B. Electroimmuno assay. Scand J Clin Lab Invest Suppl. 1972;124:21–37. doi: 10.3109/00365517209102748. [DOI] [PubMed] [Google Scholar]
  6. Lospalluto J. J., Finkelstein R. A. Chemical and physical properties of cholera exo-enterotoxin (choleragen) and its spontaneously formed toxoid (choleragenoid). Biochim Biophys Acta. 1972 Jan 26;257(1):158–166. doi: 10.1016/0005-2795(72)90265-6. [DOI] [PubMed] [Google Scholar]
  7. OUCHTERLONY O. Diffusion-in-gel methods for immunological analysis. II. Prog Allergy. 1962;6:30–154. doi: 10.1159/000313795. [DOI] [PubMed] [Google Scholar]
  8. Peterson J. W., LoSpalluto J. J., Finkelstein R. A. Localization of cholera toxin in vivo. J Infect Dis. 1972 Dec;126(6):617–628. doi: 10.1093/infdis/126.6.617. [DOI] [PubMed] [Google Scholar]
  9. SVENNERHOLM L. CHROMATOGRAPHIC SEPARATION OF HUMAN BRAIN GANGLIOSIDES. J Neurochem. 1963 Sep;10:613–623. doi: 10.1111/j.1471-4159.1963.tb08933.x. [DOI] [PubMed] [Google Scholar]
  10. Van Heyningen W. E., Carpenter C. C., Pierce N. F., Greenough W. B., 3rd Deactivation of cholera toxin by ganglioside. J Infect Dis. 1971 Oct;124(4):415–418. doi: 10.1093/infdis/124.4.415. [DOI] [PubMed] [Google Scholar]
  11. WADSWORTH C. A slide microtechnique for the analysis of immune precipitates in gel. Int Arch Allergy Appl Immunol. 1957;10(6):355–360. doi: 10.1159/000228394. [DOI] [PubMed] [Google Scholar]

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