Ganglioside toxin

Figure 14-13. G i ganglioside, a monosialoganglio-side, the receptor in human intestine for cholera toxin.

Glycosphingolipids are constituents of the outer leaflet of plasma membranes and are important in cell adhesion and cell recognition. Some are antigens, eg, ABO blood group substances. Certain gangliosides function as receptors for bacterial toxins (eg, for cholera toxin, which subsequently activates adenylyl cyclase). 

Rowe-Taitt C.A., Cras J.J., Patterson C.H., Golden J.P., Ligler F.S., A ganglioside-based assay for cholera toxin using an array biosensor, Anal. Biochem. 2000a 281 123-133. 

Fang Y., Fratos A.G., Lahiri J., Ganglioside microarrays for toxin detection, Langmuir 19 1500-1505,2003. 

A. Bemardi, L. Carrettoni, A. Grosso Ciponte, D. Montib, and S. Sonnino, Second generation mimics of ganglioside GM1 as artificial receptors for Cholera Toxin Replacement of the sialic acid moiety, Bioorg. Med. Chem. Lett., 10 (2000) 2197-2200. 

Two of the most widely spread and well-studied enterotoxigenic forms of bacterial diarrhea are ETEC and Vibrio cholerae. The toxins they produce, labile toxin (LT) and cholera toxin (CT) respectively, are very similar in primary sequence, structure, and mechanism of action [72]. They are homologous multi-subunit proteins in which the non-toxic B subunit mediates GMj ganglioside binding, and thus are candidates for vaccines that can neutralize toxin activity. 

A. A. Wolf, M. G. Jobling, S. Wimer-Mackin, M. Ferguson-Maltzman, J. L. Madara, R. K. Holmes, and W. I. Lencer. Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia. J Cell Biol. 141 917-927 (1998). 

Caveolae can mediate the delivery of CtxB that binds to GM1 ganglioside at the plasma membrane and is delivered to intracellular compartments. Cholera toxin, produced by Vibrio cholerae, consists of five identical subunits B and one A chain. In addition to labeled SV40 and caveolin-1-GFP, CtxB is one of the most commonly used caveolae markers. However, two groups reported that the toxin is internalized by either a clathrin-independent caveolae pathway or a clathrin-dependent uptake, bringing its selectivity/specificity into question (31,81,118). We controlled the suitability of this marker for COS-7 cells pretreated with CPZ, mpCD, and filipin and as expected, the uptake was not influenced by CPZ treatment but was strongly decreased by the latter two (data not shown). 

In both of these cases, the ligand (sialic acid) for the analyte of interest (influenza vims) was covalently linked to the PDA backbone generated upon photopolymerization. Functional sensors based on ligands that are noncovalently incorporated into liposomes have also been reported (Charych et al. 1996 Pan and Charych 1997). Mixed liposomes as well as mixed thin films on glass containing a combination of the ganglioside GMl and diacetylene lipids detect the presence of cholera toxin, a protein that binds to GMl. 

Pan JJ, Charych D. Molecular recognition and colorimetric detection of cholera toxin by poly (diacetylene) hposomes incorporating GMl ganglioside. Langmuir 1997 13 1365-1367. 

Mucosal adjuvants Bind to M cells and GMl ganglioside receptors on mucosal epithelium CT toxin... 

Lian, T., T. Bui, and R.J. Ho, Formulation of HFV-envelope protein with lipid vesicles expressing ganglioside GMl associated to cholera toxin B enhances mucosal immune responses. Vaccine, 1999. 18(7-8) 604-11. 

Lian, T., and R.J. Ho, Cholera toxin B-mediated targeting of lipid vesicles containing ganglioside GMl to mucosal epithelial cells. Pharm Res, 1997.14(10) 1309-15. 

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