Fragment C of tetanus toxin: new insights into its neuronal signaling pathway

Int J Mol Sci. 2012;13(6):6883-901. doi: 10.3390/ijms13066883. Epub 2012 Jun 7.

Abstract

When Clostridium tetani was discovered and identified as a Gram-positive anaerobic bacterium of the genus Clostridium, the possibility of turning its toxin into a valuable biological carrier to ameliorate neurodegenerative processes was inconceivable. However, the non-toxic carboxy-terminal fragment of the tetanus toxin heavy chain (fragment C) can be retrogradely transported to the central nervous system; therefore, fragment C has been used as a valuable biological carrier of neurotrophic factors to ameliorate neurodegenerative processes. More recently, the neuroprotective properties of fragment C have also been described in vitro and in vivo, involving the activation of Akt kinase and extracellular signal-regulated kinase (ERK) signaling cascades through neurotrophin tyrosine kinase (Trk) receptors. Although the precise mechanism of the molecular internalization of fragment C in neuronal cells remains unknown, fragment C could be internalized and translocated into the neuronal cytosol through a clathrin-mediated pathway dependent on proteins, such as dynamin and AP-2. In this review, the origins, molecular properties and possible signaling pathways of fragment C are reviewed to understand the biochemical characteristics of its intracellular and synaptic transport.

Keywords: Trk receptors; clathrin-mediated pathway; dynamin; fragment C; neurotrophin; tetanus toxin.

Publication types

  • Review

MeSH terms

  • Animals
  • Axons / metabolism
  • Clostridium tetani / metabolism
  • Cytosol / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Motor Neurons / metabolism
  • Neurons / metabolism*
  • Peptide Fragments / metabolism*
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Tetanus Toxin / metabolism*

Substances

  • Peptide Fragments
  • Tetanus Toxin
  • tetanus toxin fragment C
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinases