Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization

J. Oliver Dolly, Jennifer Black, Richard S. Williams, Jack Melling

Research output: Contribution to journalArticle

246 Scopus citations

Abstract

Botulinum neurotoxin (BoNY) type A, a causative agent of botulism, is a di-chain protein (molecular weight 140,000) from Clostridium botulinum, and the most neurotoxic substance known1. Some cases of sudden infant cot deaths have been attributed to such a neuroparalytic condition2. BoNT inhibits irreversibly the release of acetylcholine from peripheral nerves in a highly selective manner3-6. Hence, it is potentially an invaluable probe for studying the mechanism of transmitter release7,8. Here we demonstrate specific labelling of murine motor nerve terminals with neurotoxic, 125I-labelled BoNT (type A) by autoradiography. We observed saturable, temperature-sensitive binding of BoNT to sites which reside solely on the nerve terminal membrane; these were distributed on all unmyelinated areas, at an average density of 150-500 per μm2 of membrane. The binding was mediated by the larger summit of the toxin and was inhibited partially by tetanus toxin, another microbial protein9. No specific binding was detectable on any other cell types examined, including noradrenergic terminals. Following binding, internalization of radioactivity was observed; this process was energy-dependent as it could be prevented totally by aride or dinitrophenol (DNP). This direct demonstration of separable steps, including highly selective binding and acceptor-mediated internalization, is reconcilable with the unique potency and the multiphasic inhibitory action of BoNT on transmitter release, as shown electrophysiologically8.

Original languageEnglish (US)
Pages (from-to)457-460
Number of pages4
JournalNature
Volume307
Issue number5950
DOIs
StatePublished - 1984
Externally publishedYes

ASJC Scopus subject areas

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