Botulinum A neurotoxin unlike tetanus toxin acts via a neuraminidase sensitive structure

Abstract

H. Bigalke, H. Müller and F. Dreyer. Botulinum A neurotoxin unlike tetanus toxin acts via a neuraminidase sensitive structure. Toxicon 24, 1065 – 1074, 1986. — The binding and effects of tetanus and botulinum A neurotoxins were studied on mouse spinal cord cultures treated with neuraminidase. In untreated cultures both neurotoxins blocked synaptic transmission. Treatment of the cell cultures with neuraminidase, 25 mU/ml for 24 hr, decreased the potency of botulinum A neurotoxin. At 7 × 10 −11 M no toxin effect on inhibitory or excitatory synapses was observed, whereas at higher concentrations of the toxin the concentration - response curve was shifted to the right by a factor of about 30. Surprisingly, the action of tetanus toxin over a large concentration range was unaffected by pretreatment of the neurones with the enzyme. Accordingly, neurones treated with neuraminidase failed to bind 125I-botulinum A neurotoxin, whereas labelled tetanus toxin was still fixed by cell bodies, as well as by neurites, as shown by histoautoradiography. Chromatographic extraction of gangliosides from cultures prelabelled with 14C-glucosamine showed a dramatic loss in the contents of polysialogangliosides following treatment with neuraminidase. Our results indicate that neuraminidase-sensitive structures might be important for the action of botulinum A neurotoxin. The effect of tetanus toxin appears to be mediated by a different site which is insensitive to neuraminidase.