Botulinum protease-cleaved SNARE fragments induce cytotoxicity in neuroblastoma cells

摘要: Soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) are crucial for exocytosis, trafficking, and neurite outgrowth, where vesicular SNAREs directed toward their partner target SNAREs: synaptosomal-associated of 25 kDa syntaxin. SNARE proteins normally membrane bound, but can be cleaved released by botulinum neurotoxins. We found that proteases types C D easily transduced into endocrine cells using DNA-transfection reagents. Following administration the refractory Neuro2A neuroblastoma cells, were with high efficiency within hours. Remarkably, protease exposures led to cytotoxicity evidenced spectrophotometric assays propidium iodide penetration nuclei. Direct delivery fragments reduced viability similar proteases' application. observed synergistic cytotoxic effects proteases, which may explained release interaction soluble fragments. show first time previously neurotoxins/C in neurons could achieved neuroendocrine origin implications medical uses preparations. Ternary complex formation synaptobrevin (green) syntaxin/synaptosomal-associated (red) is necessary vesicle fusion, cell homeostasis. Botulinum cleave three as indicated, resulting a loss viability. Lipofection reagents used deliver or short peptides revealing