Neurospecific Binding, Internalization, and Retrograde Axonal Transport

  • J. L. Halpern
  • E. A. Neale
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 195)

Abstract

A number of pharmacologic agents which act on intracellular targets typically bind to specific cell surface receptors and are internalized in order to exert their effects on a cytosolic substrate (Neville and Chang 1978). Although many of the details remain to be determined, generally it is accepted that the clostridial neurotoxins (CNTs) interact with membrane receptors and are translocated into the cytosol where they act to block release of neurotransmitters (Habermann et al. 1980; Schmitt et al. 1981; Simpson 1980, 1981). The active toxins consist of a light (L) chain and a heavy (H) chain that are linked by one disulfide bond. The neurotoxins comprise three functional domains, each of which is required for one of the steps in the intoxication process (Fig. 1). The carboxyl terminal half of the H chain (HC) carries the receptor binding domain, the amino terminal half of the H chain (HN)
constitutes the transmembrane domain, and the L chain is the catalytic domain (reviewed by Niemann 1991; Wellhöner 1992). This chapter summarizes current data on the binding of CNTs to sensitive cells and the mechanism whereby the toxins are thought to gain access to their cytoplasmic targets.

Keywords

Toxicity Adenosine Carboxyl Serotonin Noradrenaline 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • J. L. Halpern
    • 1
  • E. A. Neale
    • 2
  1. 1.Division of Bacterial Products, Center for Biologics Evaluation and ResearchFood and Drug AdministrationBethesdaUSA
  2. 2.Laboratory of Developmental NeurobiologyNational Institute of Child Health and Human DevelopmentBethesdaUSA

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