Elsevier

NeuroToxicology

Volume 26, Issue 5, October 2005, Pages 761-767
NeuroToxicology

Review
Internalization and Mechanism of Action of Clostridial Toxins in Neurons

https://doi.org/10.1016/j.neuro.2004.12.012Get rights and content

Abstract

Botulinum toxins are metalloproteases that act inside nerve terminals and block neurotransmitter release via their activity directed specifically on SNARE proteins. This review summarizes data on botulinum toxin modes of binding, sites of action, and biochemical activities. Their use in cell biology and neuroscience is considered, as well as their therapeutic utilization in human diseases characterized by hyperfunction of cholinergic terminals.

Section snippets

INTRODUCTION

Many pathogenic bacteria produce protein toxins that act inside cells. These toxins bind to the cell surface, become internalized in vesicular compartments, and translocate their catalytic subunit into the cytosol, where they exert their toxic activity by enzymatically modifying a protein substrate (Montecucco et al., 1994). Tetanus (TeNT) and botulinum (BoNT) neurotoxins, endowed with a metalloprotease activity, belong to this group of bacterial toxins. They are released from bacteria as

Acknowledgements

Work in our laboratory is supported by Telethon GGP04196, by FISR-CNR Neurobiotecnologia 2003, by FIRB (RBNE01RHZM), by MIUR-CNR Functional Genomics and PRIN-MIUR 2003 055110-002.

References (53)

  • J. Mellanby et al.

    How does tetanus toxin act?

    Neuroscience

    (1981)
  • F.A. Meunier et al.

    Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation

    Mol Cell Neurosci

    (2003)
  • C. Montecucco et al.

    Bacterial protein toxins penetrate cells via a four-step mechanism

    FEBS Lett

    (1994)
  • C. Montecucco et al.

    Botulinum neurotoxins: mechanism of action and therapeutic applications

    Mol Med Today

    (1996)
  • C. Montecucco et al.

    Presynaptic receptor arrays for clostridial neurotoxins

    Trends Microbiol

    (2004)
  • T. Nishiki et al.

    Identification of protein receptor for Clostridium botulinum type B neurotoxin in rat brain synaptosomes

    J Biol Chem

    (1994)
  • T. Nishiki et al.

    Binding of botulinum type B neurotoxin to Chinese hamster ovary cells transfected with rat synaptotagmin II cDNA

    Neurosci Lett

    (1996)
  • A. Puhar et al.

    Comparison of the pH-induced conformational change of different clostridial neurotoxins

    Biochem Biophys Res Commun

    (2004)
  • A. Rummel et al.

    Synaptotagmins I and II act as nerve cell receptors for botulinum neurotoxin G

    J Biol Chem

    (2004)
  • C. Verderio et al.

    SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization

    Neuron

    (2004)
  • A.C. Ashton et al.

    Characterization of the inhibitory action of botulinum neurotoxin type A on the release of several transmitters from rat cerebrocortical synaptosomes

    J Neurochem

    (1988)
  • M. Bajohrs et al.

    A molecular basis underlying differences in the toxicity of botulinum serotypes A and E

    EMBO Rep

    (2004)
  • R. Benecke et al.

    Tetanus toxin induced actions on spinal Renshaw cells and Ia-inhibitory interneurones during development of local tetanus in the cat

    Exp Brain Res

    (1977)
  • H. Bigalke et al.

    Tetanus toxin and botulinum A toxin inhibit release and uptake of various transmitters, as studied with particulate preparations from rat brain and spinal cord

    Naunyn Schmiedebergs Arch Pharmacol

    (1981)
  • J.D. Black et al.

    Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis

    J Cell Biol

    (1986)
  • M. Capogna et al.

    Ca2+ or Sr2+ partially rescues synaptic transmission in hippocampal cultures treated with botulinum toxin A and C, but not tetanus toxin

    J Neurosci

    (1997)
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