Stecher, B.; Gratzl, Manfred; Ahnert-Hilger, G.
Reductive chain separation of botulinum A toxin — a prerequisite to its inhibitory action on exocytosis in chromaffin cells.
In: FEBS Letters, Vol. 248: S. 23-27
Cleavage of the disulfide bond linking the heavy and the light chains of tetanus toxin is necessary for its inhibitory action
on exocytotic release ofcatecholamines from permeabi1ized chromaffin cells [(1989) FEBS Lett. 242, 245-248; (1989) J.
Neurochern., in press]. The related botulinum A toxin also consists of a heavy and a light chain linked by a disulfide
bond. The actions ofboth neurotoxins on exocytosis were presently compared using streptolysin O-permeabilized bovine
adrenal chromaffin cells. Botulinum A toxin inhibited Ca2 +-stimulated catecholamine release from these cells. Addition
of dithiothreitollowered the effective doses to values below 5 nM. Under the same conditions, the effective doses of tetanus
toxin were decreased by a factor of five. This indicates that the interchain S-S bond of botulinum A toxin must
also be split before the neurotoxin can exert its effect on exocytosis.