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- Title
The sensitivity of catecholamine release to botulinum toxin C1 and E suggests selective targeting of vesicles set into the readily releasable pool.
- Authors
Stigliani, Sara; Raiteri, Luca; Fassio, Anna; Bonanno, Giambattista
- Abstract
Abstract The impact of syntaxin and SNAP-25 cleavage on [[sup 3]H]noradrenaline ([[sup 3]H]NA) and [[sup 3]H]dopamine ([[sup 3]H]DA) exocytotic release evoked by different stimuli was studied in superfused rat synaptosomes. The external Ca[sup 2+]-dependent K[sup +]-induced [[sup 3]H]catecholamine overflows were almost totally abolished by botulinum toxin C1 (BoNT/C1), which hydrolyses syntaxin and SNAP-25, or by botulinum toxin E (BoNT/E), selective for SNAP-25. BoNT/C1 cleaved 25% of total syntaxin and 40% of SNAP-25; BoNT/E cleaved 40% of SNAP-25 but left syntaxin intact. The GABA uptake-induced releases of [[sup 3]H]NA and [[sup 3]H]DA were differentially affected: both toxins blocked the former, dependent on external Ca[sup 2+], but not the latter, internal Ca[sup 2+]-dependent. BoNT/C1 or BoNT/E only slightly reduced the ionomycin-evoked [[sup 3]H]catecholamine release. More precisely, [[sup 3]H]NA exocytosis induced by ionomycin was sensitive to toxins in the early phase of release but not later. The Ca[sup 2+]-independent [[sup 3]H]NA exocytosis evoked by hypertonic sucrose, thought to release from the readily releasable pool (RRP) of vesicles, was significantly reduced by BoNT/C1. Pre-treating synaptosomes with phorbol-12-myristate-13-acetate, to increase the RRP, enhanced the sensitivity to BoNT/C1 of [[sup 3]H]NA release elicited by sucrose or ionomycin. Accordingly, cleavage of syntaxin was augmented by the phorbol-ester. To conclude, our results suggest that clostridial toxins selectively target exocytosis involving vesicles set into the RRP.
- Subjects
CATECHOLAMINES; BOTULINUM toxin; SYNAPSES; NEUROTRANSMITTERS; EXOCYTOSIS
- Publication
Journal of Neurochemistry, 2003, Vol 85, Issue 2, p409
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2003.01689.x