Interaction of fragments B and C of tetanus toxin with neural and thyroid membranes and with gangliosides.

Fragment C of tetanus toxin appears to retain most of the determinants of the tetanus toxin molecule insofar as interactions with neural or thyroid membranes and with gangliosides are concerned. Thus, unlabeled fragment C is nearly as effective as unlabeled tetanus toxin in inhibiting the binding of either ‘251-labeled toxin or ‘251-labeled thyrotropin to neural or thyroid membranes. ‘251-labeled fragment C interactions with neural membranes are effectively the same as ‘261-labeled tetanus toxin when studied as a function of membrane protein, salt concentration, or pH. Both bind reversibly and have the same specificity for unlabeled ligands. Both interact similarly with gangliosides whether the gangliosides are in aqueous suspensions or imbedded in liposomes, or whether examined as a function of ganglioside concentration or individual ganglioside specificity. Modulation of the lipid composition of liposomes containing gangliosides does not affect the binding of either tetanus toxin or fragment C, although it does alter thyrotropin binding. Fragment C undergoes retrograde axonal transport like tetanus toxin. In contrast to fragment C, fragment B of tetanus toxin appears to have none of the determinants of the toxin molecule important for receptor interactions in membrane binding assays. In experiments using ganglioside-containing liposomes, fragment B was also unable to inhibit the binding of tetanus toxin but was noted to slightly inhibit thyrotropin binding. Although fragment B does not undergo retrograde axonal transport, some diffuse neural uptake was noted in these assays. Unlike tetanus toxin, neither fragment C nor fragment B has any effect on the membrane potential of synaptosome preparations.