Cytotoxicity of Botulinum Neurotoxins Reveals a Direct Role of Syntaxin 1 and SNAP-25 in Neuron Survival

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Cytotoxicity of Botulinum Neurotoxins Reveals a Direct Role of Syntaxin 1 and SNAP-25 in Neuron Survival

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Title: Cytotoxicity of Botulinum Neurotoxins Reveals a Direct Role of Syntaxin 1 and SNAP-25 in Neuron Survival
Author: Peng, Lisheng; Liu, Huisheng; Ruan, Hongyu; Tepp, William H.; Stoothoff, William H.; Brown, Robert H.; Johnson, Eric A.; Yao, Wei-Dong; Zhang, Su-Chun; Dong, Min

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Citation: Peng, Lisheng, Huisheng Liu, Hongyu Ruan, William H. Tepp, William H. Stoothoff, Robert H. Brown, Eric A. Johnson, Wei-Dong Yao, Su-Chun Zhang, and Min Dong. 2014. “Cytotoxicity of Botulinum Neurotoxins Reveals a Direct Role of Syntaxin 1 and SNAP-25 in Neuron Survival.” Nature communications 4 (1): 1472. doi:10.1038/ncomms2462. http://dx.doi.org/10.1038/ncomms2462.
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Abstract: Botulinum neurotoxins (BoNT/A-G) are well-known to act by blocking synaptic vesicle exocytosis. Whether BoNTs disrupt additional neuronal functions has not been addressed. Here we report that cleavage of syntaxin 1 (Syx 1) by BoNT/C and cleavage of SNAP-25 by BoNT/E both induce degeneration of cultured rodent and human neurons. Furthermore, although SNAP-25 cleaved by BoNT/A can still support neuron survival, it has reduced capacity to tolerate additional mutations and also fails to pair with syntaxin isoforms other than Syx 1. Syx 1 and SNAP-25 are well-known for mediating synaptic vesicle exocytosis, but we found that neuronal death is due to blockage of plasma membrane recycling processes that share Syx 1/SNAP-25 for exocytosis, independent of blockage of synaptic vesicle exocytosis. These findings reveal neuronal cytotoxicity for a subset of BoNTs and directly link Syx 1/SNAP-25 to neuron survival as the prevalent SNARE proteins mediating multiple fusion events on neuronal plasma membranes.
Published Version: doi:10.1038/ncomms2462
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052923/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406680
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