Isolated light chain of tetanus toxin inhibits exocytosis: studies in digitonin-permeabilized cells.
Previous work indicates that the heavy chain of tetanus toxin is responsible for the binding of the toxin to the neuronal membrane and its subsequent internalization. In the present study, the light chain of tetanus toxin mimicked the holotoxin in inhibiting Ca2+-dependent secretion of [3H]norepinephrine from digitonin-permeabilized adrenal chromaffin cells. Preincubation of tetanus toxin with monoclonal antibodies to the light chain prevented the inhibition by tetanus toxin. Preincubation of tetanus toxin with nonimmune ascites fluid or with monoclonal antibodies directed against the C fragment (the C-terminal of the heavy chain) or the heavy-chain portion of the B fragment did not prevent inhibition by tetanus toxin. The data indicate that the light chain is responsible for the intracellular blockade of exocytosis.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
M A
MA
Bittner
W H
WH
Habig
R W
RW
Holz
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability; D002838:Chromaffin System / Q000187:drug effects / Q000378:metabolism*; D004072:Digitonin; D005089:Exocytosis; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D013744:Tetanus Toxin / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D013744:Tetanus Toxin; D004072:Digitonin; D002118:Calcium; D009638:Norepinephrine