|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 112, Issue 16 2715-2724, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
G Lalli, J Herreros, SL Osborne, C Montecucco, O Rossetto and G Schiavo
Molecular Neuropathobiology, Imperial Cancer Research Fund, London WC2A 3PX, UK.
Tetanus and botulinum neurotoxins constitute a family of bacterial protein toxins responsible for two deadly syndromes in humans (tetanus and botulism, respectively). They bind with high affinity to neurons wherein they cause a complete inhibition of evoked neurotransmitter release. Here we report on the cloning, expression and use of the recombinant fragments of the heavy chains of tetanus neurotoxin and botulinum neurotoxin serotypes A, B and E as tools to study the neurospecific binding of the holotoxins. We found that the recombinant 50 kDa carboxy-terminal domains of tetanus and botulinum neurotoxins alone are responsible for the specific binding and internalisation into spinal cord cells in culture. Moreover, we provide evidence that the recombinant fragments block the internalization of the parental holotoxins in a dose-dependent manner, as determined by following the neurotoxin-dependent cleavage of their targets VAMP/synaptobrevin and SNAP-25. In addition, the recombinant binding fragments cause a significant delay in the paralysis induced by the corresponding holotoxin on the mouse phrenic nerve-hemidiaphragm preparation. Taken together, these results show that the carboxy-terminal domain of tetanus and botulinum neurotoxins is necessary and sufficient for the binding and internalisation of these proteins in neurons and open the possibility to use them as tools for the functional characterisation of the intracellular transport of clostridial neurotoxins.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Granata, R. Watson, L. M. Collinson, G. Schiavo, and T. T. Warner The Dystonia-associated Protein TorsinA Modulates Synaptic Vesicle Recycling J. Biol. Chem., March 21, 2008; 283(12): 7568 - 7579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Eubanks, M. S. Hixon, W. Jin, S. Hong, C. M. Clancy, W. H. Tepp, M. R. Baldwin, C. J. Malizio, M. C. Goodnough, J. T. Barbieri, et al. An in vitro and in vivo disconnect uncovered through high-throughput identification of botulinum neurotoxin A antagonists PNAS, February 20, 2007; 104(8): 2602 - 2607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bracale, F. Cesca, V. E. Neubrand, T. P. Newsome, M. Way, and G. Schiavo Kidins220/ARMS Is Transported by a Kinesin-1-based Mechanism Likely to be Involved in Neuronal Differentiation Mol. Biol. Cell, January 1, 2007; 18(1): 142 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Qazi, D. Sesardic, R. Tierney, Z. Soderback, D. Crane, B. Bolgiano, and N. Fairweather Reduction of the Ganglioside Binding Activity of the Tetanus Toxin HC Fragment Destroys Immunogenicity: Implications for Development of Novel Tetanus Vaccines. Infect. Immun., August 1, 2006; 74(8): 4884 - 4891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bohnert and G. Schiavo Tetanus Toxin Is Transported in a Novel Neuronal Compartment Characterized by a Specialized pH Regulation J. Biol. Chem., December 23, 2005; 280(51): 42336 - 42344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Ahsan, G. Hajnoczky, A. B. Maksymowych, and L. L. Simpson Visualization of Binding and Transcytosis of Botulinum Toxin by Human Intestinal Epithelial Cells J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1028 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Maksymowych and L. L. Simpson Structural Features of the Botulinum Neurotoxin Molecule That Govern Binding and Transcytosis across Polarized Human Intestinal Epithelial Cells J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 633 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lalli, S. Gschmeissner, and G. Schiavo Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons J. Cell Sci., November 15, 2003; 116(22): 4639 - 4650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-B. Park and L. L. Simpson Inhalational Poisoning by Botulinum Toxin and Inhalation Vaccination with Its Heavy-Chain Component Infect. Immun., March 1, 2003; 71(3): 1147 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Yowler, R. D. Kensinger, and C.-L. Schengrund Botulinum Neurotoxin A Activity Is Dependent upon the Presence of Specific Gangliosides in Neuroblastoma Cells Expressing Synaptotagmin I J. Biol. Chem., August 30, 2002; 277(36): 32815 - 32819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Herreros, T. Ng, and G. Schiavo Lipid Rafts Act as Specialized Domains for Tetanus Toxin Binding and Internalization into Neurons Mol. Biol. Cell, October 1, 2001; 12(10): 2947 - 2960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Schiavo, M. Matteoli, and C. Montecucco Neurotoxins Affecting Neuroexocytosis Physiol Rev, April 1, 2000; 80(2): 717 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fotinou, P. Emsley, I. Black, H. Ando, H. Ishida, M. Kiso, K. A. Sinha, N. F. Fairweather, and N. W. Isaacs The Crystal Structure of Tetanus Toxin Hc Fragment Complexed with a Synthetic GT1b Analogue Suggests Cross-linking between Ganglioside Receptors and the Toxin J. Biol. Chem., August 17, 2001; 276(34): 32274 - 32281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, P. Foran, G. Lawrence, N. Mohammed, C.-K.-N. Chan-Kwo-Chion, G. Lisk, R. Aoki, and O. Dolly Recombinant Forms of Tetanus Toxin Engineered for Examining and Exploiting Neuronal Trafficking Pathways J. Biol. Chem., August 10, 2001; 276(33): 31394 - 31401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lalli and G. Schiavo Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75NTR J. Cell Biol., January 21, 2002; 156(2): 233 - 240. [Abstract] [Full Text] [PDF]
|
|
