Traffic of botulinum toxins A and E in excitatory and inhibitory neurons

Claudia Verderio, Carlotta Grumelli, Luca Raiteri, Silvia Coco, Silvio Paluzzi, Paola Caccin, Ornella Rossetto, Giambattista Bonanno, Cesare Montecucco, Michela Matteoli

Research output: Contribution to journalArticle

Abstract

Botulinum neurotoxins (BoNTs), proteases specific for the SNARE proteins, are used to study the molecular machinery supporting exocytosis and are used to treat human diseases characterized by cholinergic hyperactivity. The recent extension of the use of BoNTs to central nervous system (CNS) pathologies prompted the study of their traffic in central neurons. We used fluorescent BoNT/A and BoNT/E to study the penetration, the translocation and the catalytic action of these toxins in excitatory and inhibitory neurons. We show that BoNT/A and BoNT/E, besides preferentially inhibiting synaptic vesicle recycling at glutamatergic relative to Gamma-aminobutyric acid (GABA)-ergic neurons, are more efficient in impairing the release of excitatory than inhibitory neurotransmitter from brain synaptosomes. This differential effect does not result from a defective penetration of the toxin in line with the presence of the BoNT/A receptor, synaptic vesicle protein 2 (SV2), in both types of neurons. Interestingly, exogenous expression of SNAP-25 in GABAergic neurons confers sensitivity to BoNT/A. These results indicate that the expression of the toxin substrate, and not the toxin penetration, most likely accounts for the distinct effects of the two neurotoxins at the two types of terminals and support the use of BoNTs for the therapy of CNS diseases caused by the altered activity of selected neuronal populations.

Original languageEnglish
Pages (from-to)142-153
Number of pages12
JournalTraffic
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 2007

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Keywords

  • Botulinum toxins
  • Excitatory/inhibitory neurons
  • Exocytosis
  • GABA
  • Glutamate
  • SNAP-25
  • SNAREs
  • Synaptic vesicles
  • Synaptosomes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Verderio, C., Grumelli, C., Raiteri, L., Coco, S., Paluzzi, S., Caccin, P., Rossetto, O., Bonanno, G., Montecucco, C., & Matteoli, M. (2007). Traffic of botulinum toxins A and E in excitatory and inhibitory neurons. Traffic, 8(2), 142-153. https://doi.org/10.1111/j.1600-0854.2006.00520.x