Role of gangliosides in the uptake and retrograde axonal transport of cholera and tetanus toxin as compared to nerve growth factor and wheat germ agglutinin

Abstract

Previous investigations have shown that tetanus toxin is transported retrogradely in all peripheral neurons whereas the transport of NGF is confined to adrenergic and sensory neurons. Other macromolecules with molecular weights and general physiochemical properties of similar to NGF and tetanus toxin (e.g., cytochrome C, insulin, horseradish peroxidase and bovine serum albumin) are not transported to a detectable extent if injected in comparable molar concentrations. For tetanus toxin, which is transported in all peripheral neurons, it has to be assumed that it's retrograde transport depends on properties common to all neurons. In view of the relatively high ganglioside content of the neurons and the high affinity of tetanus toxin for the trisialoganglioside G T1, we studied the influence of gangliosides on the retrograde transport of tetanus toxin as compared to NGF. We included into the study cholera toxin which is known to have a high affinity for the monosialoganglioside G M1 and wheat germ agglutinin, a lectin with specific affinity for glycoproteins with N-acetyl-glucosamine residues. Both cholera toxin and wheat germ agglutinin were transported efficiently in all peripheral neurons. Preincubation of 125I-cholera toxin with monosialoganglioside G M1 completely blocked its retrograde axonal transport. The transport of NGF and wheat germ agglutinin was affected neither by various purified gangliosides nor by a mixture of bovine brain gangliosides. The transport of tetanus toxin was only reduced by 50% both by the trisialoganglioside G T1 and the bovine ganglioside mixture.