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Ahnert-Hilger, G. and Weller, U. and Dauzenroth, M. E. and Habermann, E. and Gratzl, Manfred (1989): The tetanus toxin light chain inhibits exocytosis. In: FEBS Letters, Vol. 242: pp. 245-248
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Abstract

Tetanus toxin is one of the most poisonous substances known. It is first produced by Clostridium tetani as a single-chain protein [1,2]. Subsequent proteolytic processing leads to a pharmacologically more active [3], two-chain form consisting of disulfide-linked heavy (98 kDa) and light (53 kDa) chains. The individual chains alone produced by reduction are not neurotoxic [4]. Intoxication requires hours before transmitter release is blocked. This delay reflects the time required for the binding of the toxin to the plasma membrane and its subsequent internalization before the toxin can interact with its as yet unknown intracellular target (cf. [2]). Adrenal medullary chromaffin cells, closely related to neurones, lack the capacity to bind tetanus toxin [2] and therefore are insensitive to externally applied toxin [5,6]. Sensitivity may be introduced by pretreatment of such cells with a ganglioside mixture containing tri- and tetrasialogangliosides as putative receptors (Marxen, Fuhrmann and Bigalke, personal communication). When directly injected into these cells tetanus toxin inhibits Ca2+ -induced exocytosis as revealed by cell capacitance measurement [7]. Binding and internalization can be by-passed using permeabilized cell preparations. With these methods the cytoplasm becomes fully accessible to extrinsic substances including Ca2+, drugs and toxins. Pheochromocytoma (PC 12) or adrenal medullary chromaffin cells in culture, when permeabilized with pore-forming proteins (cf. [8]) still release catecholamines in response to micromolar concentrations of Ca2 + [9-13]. Cells can be made permeable to low molecular mass solutes with staphylococcal er-toxin [9-14] and to large proteins such as immunoglobulins with streptolysin 0 (SLO) [8,13,15]. We have recently looked for an interference of various forms of tetanus toxin or its chains with the Ca2+ -stimulated [3H]noradrenaline release from SLO-permeabilized chromaffin cells.