Cleaved intracellular SNARE peptides are implicated in a novel cytotoxicity mechanism of botulinum serotype C

Arsenault, Jason, Cuijpers, Sabine A. G., Ferrari, Enrico, Niranjan, Dhevahi, O'Brien, John A. and Davletov, Bazbek (2013) Cleaved intracellular SNARE peptides are implicated in a novel cytotoxicity mechanism of botulinum serotype C. In: 23rd American Peptide Symposium, June 22 – 27, 2013, Hilton Waikoloa Village on the Big Island of Hawai‘i.

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Item Type:Conference or Workshop contribution (Paper)
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Abstract

Recent advances in intracellular protein delivery have enabled more in-depth analyses of
cellular functions. A specialized family of SNARE proteases, known as Botulinum
Neurotoxins, blocks neurotransmitter exocytosis, which leads to systemic toxicity caused by
flaccid paralysis. These pharmaceutically valuable enzymes have also been helpful in the
study of SNARE functions. As can be seen in Figure 1A, SNARE bundle formation causes
vesicle docking at the presynapse. Although these toxins are systemically toxic, no known
cytotoxic effects have been reported with the curious exception of the Botulinum serotype C
[1]. This enzyme cleaves intracellular SNAP25, as does serotype A and E, but also,
exceptionally, cleaves Syntaxin 1. Using an array of lipid and polymer transfection reagents
we were able to deliver different combinations of Botulinum holoenzymes into the normally
unaffected, Neuro2A, SH-SY5Y, PC12, and Min6 cells to analyze the individual
contribution of each SNARE protein and their cleaved peptide products.

Keywords:Peptides
Subjects:C Biological Sciences > C741 Medical Biochemistry
Divisions:College of Science > School of Life Sciences
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ID Code:12852
Deposited On:06 Jan 2014 09:09

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