Toxins, binding to gangliosides 288

Helting, T.B. Zwisler, 0. Wiegandt, H. Structure of tetanus toxin. II. Toxin binding to ganglioside. J. Biol. Chem., 1977,... 

Gangliosides are receptors for specific agents, such as cholera toxin and influenza virus. Cholera toxin binds to ganglioside GMl, whereas influenza virus recognizes the sialic acid portion of certain gangliosides. The influenza virus then cleaves the gangliosides as part of its entry process into cells. 

We consider here some pathologies of the G-protein-dependent signal pathways. Let us first consider the mechanism of action of the cholera toxin, secreted by the intestinal bacterium Vibrio cholera. Cholera is an acute diarrheal disease that can be life threatening. It causes voluminous secretion of electrolytes and fluids from the intestines of infected persons. The cholera toxin, choleragen, is a protein composed of two functional units—a B subunit that binds to gangliosides of the intestinal epithelium and a catalytic A subunit that enters the cell. The A subunit... 

It should also be mentioned that several bacterial toxins are known which bind to gangliosides in a sialic-acid-dependent manner, e.g. cholera, pertussis and tetanus toxins... 

A bacterial enterotoxin related to cholera toxin is also a target for a multivalent inhibitor. When ingested, the enterotoxin s five identical binding sites recognize and bind to ganglioside carbohydrate groups in the gut lining (163). 

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. 

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

Cholera toxin consists of one 240-residue A subunit and a ring of five 103-residue B subunits.c e The latter is a "targeting complex," a bacterial lectin each subunit of which binds to the galactose and sialic acid termini of a single molecule of ganglioside Gm1. 

Chemical modifications of cholera toxins by means of various reagents were consistently found to affect binding to cells and to GM1 ganglioside to the same extent (lU). 

Kirkpatrick LL, Matzuk MM, Dodds DC, Perin MS (2000) Biochemical interactions of the neuronal pentraxins. Neuronal pentraxin (NP) receptor binds to taipoxin and taipoxin-associated calcium-binding protein 49 via NP1 and NP2. J Biol Chem 275 17786-92 Kitamura M, Igimi S, Furukawa K, Furukawa K (2005) Different response of the knockout mice lacking b-series gangliosides against botulinum and tetanus toxins. Biochim Biophys Acta 1741 1-3... 

Choleratoxin is an enterotoxin produced by the bacterium Vibrio cholerae. On infection, one of the toxin s subunits, the B subunit binds to a ganglioside, GMl, in the membrane of sensitive cells. On binding, the other subunit. A, is released. The A subunit is an ADP-ribosyltransferase which transfers ADP-ribose from NAD+ to the... 

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