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Medizin - Open Access LMU - Teil 07/22 Podcast
The tetanus toxin light chain inhibits exocytosis

The tetanus toxin light chain inhibits exocytosis

Medizin - Open Access LMU - Teil 07/22 vor 37 Jahren

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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.