The 26-mer peptide released from SNAP-25 cleavage by botulinum neurotoxin E inhibits vesicle docking

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• 作者：Ferrer-Montiel ; Antonio V. ; et. al.
• 关键词：SNARE hypothesis ; Neurosecretion ; Exocytosis ; Synaptic transmission ; Protein-protein interaction ; BoNT ; botulinum neurotoxin ; SNAP-25 ; synaptosomal associated protein of 25 kDa ; ESUP ; excitation-secretion uncoupling peptide ; VAMP ; vesicle associated membr
• 刊名：FEBS Letters
• 出版年：1998
• 出版时间：September 11, 1998
• 年：1998
• 卷：435
• 期：1
• 页码：84-88
• 全文大小：170 K

文摘

Botulinum neurotoxin E (BoNT E) cleaves SNAP-25 at the C-terminal domain releasing a 26-mer peptide. This peptide product may act as an excitation-secretion uncoupling peptide (ESUP) to inhibit vesicle fusion and thus contribute to the efficacy of BoNT E in disabling neurosecretion. We have addressed this question using a synthetic 26-mer peptide which mimics the amino acid sequence of the naturally released peptide, and is hereafter denoted as ESUP E. This synthetic peptide is a potent inhibitor of Ca²⁺-evoked exocytosis in permeabilized chromaffin cells and reduces neurotransmitter release from identified cholinergic synapses in in vitro buccal ganglia of Aplysia californica. In chromaffin cells, both ESUP E and BoNT E abrogate the slow component of secretion without affecting the fast, Ca²⁺-mediated fusion event. Analysis of immunoprecipitates of the synaptic ternary complex involving SNAP-25, VAMP and syntaxin demonstrates that ESUP E interferes with the assembly of the docking complex. Thus, the efficacy of BoNTs as inhibitors of neurosecretion may arise from the synergistic action of cleaving the substrate and releasing peptide products that disable the fusion process by blocking specific steps of the exocytotic cascade.