Heterologous combinations of heavy and light chains from botulinum neurotoxin A and tetanus toxin inhibit neurotransmitter release in Aplysia.
The neuroparalytic activities of botulinum neurotoxin type A (BoNT A), tetanus toxin (TeTx), or homologous and heterologous combinations of their constituent polypeptides were examined at cholinergic and non-cholinergic synapses of Aplysia californica. When applied extracellularly, BoNT A or a mixture of its heavy (HC) and light (LC) chains were far more potent in blocking transmitter release at cholinergic than non-cholinergic synapses. The reverse was true for TeTx or a mixture its constituent chains. Such selectivity was assigned to differences in neuronal targetting and uptake of the neurotoxins since both exhibited similar potencies when injected directly into the cell body of either cell type. When bath-applied, heterologous combinations of the toxins' HC and LC appeared as effective as the parent neurotoxins from whence each HC was derived. Moreover, targetting/internalization was attributable to the analogous N-terminal moieties, H2 and beta 2, of the HC from BoNT A and TeTx. Thus, it may be postulated that the latter regions possess two functional domains, one being distinct and responsible for the divergent neuronal specificity, whereas the other serves a common role in translocating the LC of either toxin. Also, it was shown that the C-terminal portion of the HC of TeTx is unable to play the intracellular role of its counterpart in BoNT A.
Poulain
B
B
Laboratoire de Neurobiologie Cellulaire et Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Mochida
S
S
Weller
U
U
Högy
B
B
Habermann
E
E
Wadsworth
J D
JD
Shone
C C
CC
Dolly
J O
JO
Tauc
L
L
D000818:Animals; D001048:Aplysia; D001905:Botulinum Toxins / Q000737:chemistry / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D013744:Tetanus Toxin / Q000737:chemistry / Q000494:pharmacology*
D018377:Neurotransmitter Agents; D013744:Tetanus Toxin; D001905:Botulinum Toxins