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Syntaxin and 25‐kDa synaptosomal‐associated protein: Differential effects of botulinum neurotoxins C1 and A on neuronal survival
Author(s) -
Williamson Lura C.,
Neale Elaine A.
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19980601)52:5<569::aid-jnr9>3.0.co;2-a
Subject(s) - syntaxin , neurite , neurodegeneration , neuroscience , microbiology and biotechnology , synaptophysin , biology , clostridium botulinum , synaptic vesicle , neuron , chemistry , exocytosis , biochemistry , immunology , medicine , toxin , vesicle , immunohistochemistry , disease , membrane , secretion , in vitro
The Clostridium botulinum neurotoxins (BoNTs) A and C1 cleave specific proteins required for neuroexocytosis. We demonstrated that, in intact neurons, BoNT A cleaves 25‐kDa synaptosomal‐associated protein (SNAP‐25), and BoNT C1 cleaves both syntaxin and SNAP‐25 (Williamson et al.: Mol Biol Cell 6:61a, 1995; J Biol Chem 271:7694–7699, 1996). Here, we compare the actions of BoNT A and BoNT C1 on mature and developing mouse spinal cord neurons in cell culture and demonstrate that BoNT C1 is severely neurotoxic. In mature cultures, synaptic terminals become enlarged shortly after BoNT C1 exposure, and, subsequently, axons, dendrites, and cell bodies degenerate. Electron microscopy confirms that early degenerative changes occur in synaptic terminals when the somatic cytoplasm appears normal. In newly plated cultures, few neurons survive exposure to BoNT C1. Whereas both BoNT A and BoNT C1 cleave SNAP‐25, BoNT A has no adverse effect on neurite outgrowth, synaptogenesis, or neuron survival. This cytotoxicity is unique to BoNT C1, is specific to neurons, and is initiated at the synaptic terminal, suggesting either a novel role for syntaxin or additional actions of BoNT C1. The neurodegeneration induced by BoNT C1 may be significant in terms of its efficacy for the clinical treatment of dystonia and spasticity. J. Neurosci. Res. 52:569–583, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.