Tetanus Toxin Biotinylation and Localization of Binding Sites in Catecholaminergic Cultures and Granules

  • Philip Lazarovici
  • Alexander Fedinec
  • Bernard Bizzini


Tetanus toxin (TT), the 150-kD protein secreted by Clostridium tetani bacteria, is a very powerful neurotoxin which produces spastic paralysis and death in humans in the range of ng/ kg body weight.1 The pharmacokinetics of TT entry to the central nervous system target2include the following main steps: (1) selective binding of TT on the surface of the peripheral motor neuron terminals;3 (2) TT internalization into a vesicular compartment which delivers TT by retrograde axonal transport to the spinal cord perikarya and dendrites;4 (3) TT release from the motor neuron in the spinal cord;5 (4) trans-synaptic transfer of TT and uptake into the presynaptic terminals of the inhibitory intemeurons.5 (5) Thereafter, the constitutive release of gamma amino butyric acid and/or glycine is blocked, resulting with a syndrome of motor neuron dysinhibition;6 (6) the results are muscular spastic contractions, spasms, and convulsive seizures leading to musculature rigidity, respiratory failure, and death.7 It is believed that the binding of TT to neuronal G 1 b polysialogangliosides is involved in these pharmacokinetic steps and is the initial step triggering axonal transport and inhibition of neurotransmitter release.8–9 For many years this TT-specific recognition has been used as a diagnostic and basic research tool for marking central and peripheral neuronal,10 as well as neurosecretory cells such as thyroid C, anterior pituitary, pancreatic islet cells, and derived tumors (insulinoma, pheochromocytoma, neuroblastoma).11–13 All these cells express on their surface G1b polysialogangliosides of different sugar compositions, therefore binding TT.


PC12 Cell Nerve Growth Factor Gold Particle Neurite Outgrowth Chromaffin Cell 


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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Philip Lazarovici
    • 1
  • Alexander Fedinec
    • 2
  • Bernard Bizzini
    • 3
  1. 1.Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.Department of Anatomy and NeurobiologyUniversity of TennesseeMemphisUSA
  3. 3.Department of Molecular ToxinologyInstitut PasteurParisFrance

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