Tetanus toxin: Immunocytochemical evidence for retrograde transport

Carroll, P.; Price, Donald L.; Griffin, John W.; Morris, James R.

doi:10.1016/0304-3940(78)90145-3

Cited by 18 publications

(4 citation statements)

References 21 publications

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“…Whether the compartments are true sER membranes or whether they are derived from the surface membrane and contain the ligand still bound to its membrane receptor has not been decided yet, although the latter possibility seems to be more probable (14,24). All the ligands reach the cell bodies as chemically intact molecules (9,14,15,54), and for NGF it has been shown that specific induction of tyrosine hydroxylase, an enzyme catalysing the rate-limiting step in the synthesis of the adrenergic transmitter noradrenaline, can be produced by the retrogradely transported NGF (37,38). Fusion with lysosomes and progressive degradation seems to be the fate of NGF, cholera toxin, the lectins, and also of those tetanus toxin molecules which are not released by the dendrites.…”

Section: Discussionmentioning

confidence: 99%

Selective retrograde transsynaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport

Schwab¹,

Suda²,

Thoenen³

1979

The Journal of Cell Biology

220

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The fate of tetanus toxin (mol wt 150,000) subsequent to its retrograde axonal transport in peripheral sympathetic neurons of the rat was studied by both electron microscope autoradiography and cytochemistry using toxin-horseradish peroxidase (HRP) coupling products, and compared to that of nerve growth factor (NGF), cholera toxin, and the lectins wheat germ agglutinin (WGA), phytohaemagglutinin (PHA), and ricin . All these macromolecules are taken up by adrenergic nerve terminals and transported retrogradely in a selective, highly efficient manner . This selective uptake and transport is a consequence of the binding of these macromolecules to specific receptive sites on the nerve terminal membrane .All these ligands are transported in the axons within smooth vesicles, cisternae, and tubules . In the cell bodies these membrane compartments fuse and most of the transported macromolecules are finally incorporated into lysosomes . The cell nuclei, the parallel Golgi cisternae, and the extracellular space always remain unlabeled . In the case of tetanus toxin, however, a substantial fraction of the labeled material appears in presynaptic cholinergic nerve terminals which innervate the labeled ganglion cells . In these terminals tetanus toxin-HRP is localized in 500-1,000 A Diam vesicles . In contrast, such a retrograde transsynaptic transfer is not at all or only very rarely detectable after retrograde transport of cholera toxin, NGF, WGA, PHA, or ricin . An atoxic fragment of the tetanus toxin, which contains the ganglioside-binding site, behaves like intact toxin . With all these macromolecules, the extracellular space and the glial cells in the ganglion remain unlabeled . We conclude that the selectivity of this transsynaptic transfer of tetanus toxin is due to a selective release of the toxin from the postsynaptic dendrites . This release is immediately followed by an uptake into the presynaptic terminals .KEY WORDS retrograde transport transsynaptic transfer -uptake and release of macromolecules -tetanus toxin -lectins

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Section: Discussionmentioning

confidence: 99%

Selective retrograde transsynaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport

Schwab¹,

Suda²,

Thoenen³

1979

The Journal of Cell Biology

220

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“…Locally produced and systemically circulating toxin diffuses through the internal spaces in muscle; the carboxy terminal of the heavy chain binds to ganglioside-containing receptors on membranes of nerve terminals. The toxin is taken up into these terminals by receptor-mediated endocytosis and is carried by retrograde axonal transport to motor neurons (13,88,91,92). Once the toxin reaches neurons in the brainstem and spinal cord, it passes transsynaptically to bind to synaptic terminals located on penkarya of these nerve cells (90).…”

Section: Tetattiismentioning

confidence: 99%

Neuronal Disorders: Studies of Animal Models and Human Diseases

et al. 1990

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ABSTRAC~The peripheral nervous system and the central nervous system (CNS) are comprised of assemblies of neurons that communicate via electrical and chemical signals. Different disease processes selectively affect specific populations of neurons and/or specific cell functions (i.e., "selective vulnerability" of neurons is a principal determinant of phenotypes of disease). New cellular and molecular biological approaches have begun to clarify some of the mechanisms of selective cell injury in human diseases and their animal models. Following a brief review of the normal biology of nerve cells, we use illustrations drawn from studies of experimental and human diseases to discuss the mechanisms of structurallchemical abnormalities that occur in a variety of neuronal disorders.

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“…Released by sporing organisms at the site of infection, tetanus toxin is taken up at neuromuscular junctions and passes to its site of action in the central nervous system by a process known as retrograde axonal transport (see review by van Heyningen 1980). This can be demonstrated by immunofluorescence and radioautography (Price et al 1975;Carroll et al 1978). Uptake of the toxin by the axon could depend on the high specificity of tetanus toxin for the gangliosides GTj and GDlb present in the membrane at the motor nerve ending (Stockel et al 1977); entry of toxin may be by endocytosis with subsequent transport of toxin with endocytic vessels.…”

Section: Tetanus Toxinmentioning

confidence: 99%

Host damage from bacterial toxins

Arbuthnott

Rutter²,

Glynn³

1983

Phil. Trans. R. Soc. Lond. B

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Bacterial infection often involves toxin-mediated damage to the host. This can occur at mucosal epithelial surfaces, in subepithelial tissues (involving connective tissue, blood vessels and host defence cells), or at organ or tissue sites distant from the focus of infection. This paper deals with host damage at each of these levels and examples have been selected of toxins that have a well defined role in pathogenesis and for which evidence is less clear cut. Current views of mechanisms of host damage are presented along with summaries of mode of action at the molecular level where this is known. Certain unifying features of mechanisms of toxin action on host cells are emphasised. Modern genetic methods and gene cloning techniques should help in the assessment of the role of individual toxic factors where pathogenesis is multifactorial, and preliminary examples of this approach are mentioned. The search for new toxins continues and this is illustrated with reference to the toxins involved in the staphylococcal scalded skin syndrome and staphylococcal toxic shock syndrome. This overview is intended to convey an impression of the rapid development that has taken place in knowledge of the role of toxins in pathogenesis.

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Tetanus toxin: Immunocytochemical evidence for retrograde transport

Cited by 18 publications

References 21 publications

Selective retrograde transsynaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport

Selective retrograde transsynaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport

Neuronal Disorders: Studies of Animal Models and Human Diseases

Host damage from bacterial toxins

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