BLOCKAGE OF TOXIN-CELL INTERACTIONS BY OLIGOSACCHARIDES

Project: Research project

Project Details

Description

The overall goal of this proposal is to understand how clostridial
neurotoxins interact with their target cells and to use this knowledge
to develop effective inhibitors of the toxin-cell interaction. Three
botulinum toxins (A,B and E) will be studied to determine whether
observations made with one toxin (botulinum toxin A) might have general
applicability. If the botulinum toxins behave similarly, comparisons
will be made to tetanus toxin to determine what similarities exist
between the two classes of neurotoxins. Specifically, studies of the
binding of botulinum toxins B and E to G1b gangliosides and derivatives
thereof will be carried out. Results will be compared to those obtained
for botulinum toxin A and tetanus toxin. Accumulating evidence suggests
that gangliosides may not be the only cell surface receptor for these
neurotoxins. In recent studies, we have found that botulinum toxin A,
its heavy chain and the carboxy terminal half of the heavy chain bind to
synaptosomal proteins. Tetanus toxin also adhered to synaptosomal
proteins but it had to be preincubated with GT1b in order to bind to
protein. The protein adhered to by both neurotoxins has an apparent
molecular weight of approximately 77 kDa and is glycosylated.
Experiments designed to purify and characterize the approximately kDa
protein will be continued, and the site(s) adhered to by the toxin will
be identified as will the portion of the neurotoxin responsible for the
binding, and in in vitro experiments designed to identify the functional
aspects of specific interactions.
StatusFinished
Effective start/end date1/1/906/30/95

Funding

  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases

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