Interaction between Clostridium botulinum neurotoxin and gangliosides

Abstract

The effect of gangliosides on Clostridium botulinum type A neurotoxin was examined in terms of detoxification. The molar concentrations of gangliosides necessary to detoxify 50% of 1 M Cl. botulinum neurotoxin were as follows: G M1, 2073; G M2, 2439; G M3, 6098; G D1a, 610; G D1b, 488; G T1a, 829; G T1b 6 and G Q1b, 27. Inhibition by gangliosides of the neurotoxin binding to synaptosomes showed that G T1b was highly effective, but the others were not. Low-temperature treatment inhibited the detoxification of neurotoxin by G T1b and the binding of 125I-labelled neurotoxin to the synaptosome fraction. 125I-labelled neurotoxin was mixed with G M1 or G T1b and their molecular size was estimated by sucrose-density-gradient centrifugation. When 125I-labelled neurotoxin was incubated with G M1, a single radioactive peak having a sedimentation coefficient of 7.3 S appeared. When incubated with G T1b, however, 125I-labelled neurotoxin gave three peaks having sedimentation coefficients 14, 10 and 7.3 S, respectively. The present results indicated that the location and the number of sialic acids in ganglioside molecules are of significance in the detoxification and the binding of Cl. botulinum neurotoxin with ganglioside molecules.