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Quantal Neurotransmitter Release and the Clostridial Neurotoxins’ Targets

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Clostridial Neurotoxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 195))

Abstract

The eight clostridial neurotoxins so far known, tetanus toxin (TeNT) and botulinum neurotoxins (BoNTs) types A-G, have been extensively studied, not only because they are responsible for the clinical manifestations of tetanus and botulism, but also because they have the unique ability to effectively block neurotransmitter release from nerve terminals in a long-lasting manner (for reviews see Mellanby and Green 1981; Simpson 1986; Habermann and Dreyer 1986; Sellin 1987; Dreyer 1989; Niemann 1991; Poulain and Molgó 1992; Dolly 1992; Wellhöner 1992).

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References

  • Bauerfeind R, Régnier-Vigouroux A, Fiatmark T, Huttner WB (1993) Selective storage of acetylcholine, but not catecholamines, in neuroendocrine synaptic-like microvesicles of early endosomal origin. Neuron 11: 105–121

    Article  PubMed  CAS  Google Scholar 

  • Bauerfeind R, Huttner WB, Almers VV, Augustine GJ (1994) Quantal neurotransmitter release from early endosomes. Trends Cell Biol 4: 155–156

    Article  PubMed  CAS  Google Scholar 

  • Bevan S, Wendon LM (1984) A study of the action of tetanus toxin at rat soleus neuromuscular junctions. J Physiol (Lond) 348: 1–17

    CAS  Google Scholar 

  • Bigalke H, Dreyer F, Bergey G (1985) Botulinum A neurotoxin inhibits non-cholinergic synaptic transmission in mouse spinal cord neurons in culture. Brain Res 360: 318–324

    Article  PubMed  CAS  Google Scholar 

  • Binz T, Blasi J, Yamasaki S, Baumeister A, Link E, Südhof TC, Jahn R, Niemann H (1994) Proteolysis of SNAP-25 by types E and A botulinal neurotoxins. J Biol Chem 269: 1617–1620

    PubMed  CAS  Google Scholar 

  • Blasi J, Chapman ER, Link E, Binz T, Yamasaki S, De Camilli P, Südhof TC, Niemann H, Jahn R (1993a) Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 365: 160–163

    Article  PubMed  CAS  Google Scholar 

  • Blasi J, Chapman ER, Yamasaki S, Binz T, Niemann H, Jahn R (1993b) Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. EMBO J 12: 4821–4828

    PubMed  CAS  Google Scholar 

  • Boroff DA, del Castillo J, Evoy WH, Steinhardt RA (1974) Observations on the action of type A botulinum toxin on frog neuromusuclar junctions. J Physiol (Lond) 240: 227–253

    CAS  Google Scholar 

  • Cull-Candy SG, Lundh H, Thesleff S (1976) Effects of botulinum toxin on neuromuscular transmission in the rat. J Physiol (Lond) 260: 177–203

    CAS  Google Scholar 

  • DeCamilli P, Jahn R (1990) Pathways to regulated exocytosis in neurons. Annu Rev Physiol 52: 625–645

    Article  CAS  Google Scholar 

  • De Paiva A, Ashton AC, Foran P, Schiavo G, Montecucco C, Dolly JO (1993) Botulinum A like type B and tetanus toxin fulfils criteria for being a zinc-dependent protease. J Neurochem 61: 2338–2341

    Article  PubMed  Google Scholar 

  • Dolly JO (1992) Peptide toxins that alter neurotransmitter release. In: Herken H, Hucho F (eds) Selective neurotoxicity. Springer, Berlin Heidelberg New York, pp 681–717 (Handbook of experimental pharmacology, vol 102)

    Google Scholar 

  • Dolly JO, Lande S, Wray W (1987) The effects of in vitro application of purified botulinum neurotoxin at mouse motor nerve terminals. J Physiol (Lond) 386: 475–484

    CAS  Google Scholar 

  • Dreyer F (1989) Peripheral actions of tetanus toxin. In: Simpson LL (ed) Botulinum neurotoxin and tetanus toxin. Academic, San Diego, pp 179–202

    Google Scholar 

  • Dreyer F, Schmitt A (1981) Different effects of botulinum A toxin and tetanus toxin on the transmitter releasing process at the mammalian neuromuscular junction. Neurosci Lett 26: 307–311

    Article  PubMed  CAS  Google Scholar 

  • Dreyer F, Schmitt A (1983) Transmitter release in tetanus and botulinum A toxin-poisoned mammalian motor end-plates and its dependence on nerve stimulation and temperature. Pflugers Arch 399: 228–234

    Article  PubMed  CAS  Google Scholar 

  • Dreyer F, Mallart A, Brigant JL (1983) Botulinum A toxin and tetanus toxin do not affect presynaptic membrane currents in mammalian motor nerve endings. Brain Res 270: 373–375

    Article  PubMed  CAS  Google Scholar 

  • Dreyer F, Rosenberg F, Becker C, Bigalke H, Penner R (1987) Differential effects of various secretagogues on quantal transmitter release from mouse motor nerve terminals treated with botulinum A and tetanus toxin. Naunyn Schmiedeberg’s Arch Pharmacol 335: 1–7

    Article  CAS  Google Scholar 

  • Duchen LW, Tonge DA (1973) The effects of tetanus toxin on neuromuscular transmission and on the morphology of motor endplates in slow and fast skeletal muscle of the mouse. J Physiol (Lond) 228: 157–172

    CAS  Google Scholar 

  • Dunant Y, Esquerda JE, Loctin F, Marsal J, Müller D (1987) Botulinum toxin inhibits quantal acetylcholine release and energy metabolism in Torpedo electric organ. J Physiol (Lond) 385: 677–692

    CAS  Google Scholar 

  • Facchiano F, Luini A (1992) Tetanus toxin potently stimulates tissue transglutaminase a possible mechanism of neurotoxicity. J Biol Chem 267: 13267–13271

    PubMed  CAS  Google Scholar 

  • Facchiano F, Benfenati F, Valtorta F, Luini A (1993) Covalent modification of synapsin I by a tetanus toxin-activated transglutaminase. J Biol Chem 268: 4588–4591

    PubMed  CAS  Google Scholar 

  • Galli T, Chilcote T, Mundigl O, Binz T, Niemann H, De Camilli P (1994) Tetanus toxin-mediated cleavage of cellubrevin impairs exocytosis of transferrin receptor-containing vesicles in CHO cells. J Cell Biol 125: 1015–1024

    Article  PubMed  CAS  Google Scholar 

  • Gansel M, Penner R, Dreyer F (1987) Distinct sites of action of clostridial neurotoxins revealed by double poisoning of mouse motor nerve terminals. Pflugers Arch 409: 533–539

    Article  PubMed  CAS  Google Scholar 

  • Gundersen CB (1980) The effects of botulinum toxin on the synthesis, storage and release of acetylcholine. Prog Neurobiol 4: 99–119

    Article  Google Scholar 

  • Gundersen CB, Katz B, Miledi R (1982) The antagonism between botulinum toxin and calcium in motor nerve terminals. Proc R Soc Lond [Biol] 216: 369–376

    Article  CAS  Google Scholar 

  • Habermann E, Dreyer F (1986) Clostridial neurotoxins: handling and action at the cellular and molecular level. In: Capron A, Compans RW, Cooper M et al. (eds) Current topics in microbiology and immunology, vol 129. Springer, Berlin Heidelberg New York, pp 93–179

    Chapter  Google Scholar 

  • Harris AJ, Miledi R (1971) The effect of type D botulinum toxin on frog neuromuscular junctions. J Physiol (Lond) 217: 497–515

    CAS  Google Scholar 

  • Hata Y, Davletov B, Petrenko AG, Jahn R, Südhof TC (1993) Interaction of synaptotagmin with the cytoplasmic domain of neurexins. Neuron 10: 307–315

    Article  PubMed  CAS  Google Scholar 

  • Kanda K, Takano K (1983) Effect of tetanus toxin on the excitatory and the inhibitory post-synaptic potentials in the cat motoneurone. J Physiol (Lond) 335: 319–333

    CAS  Google Scholar 

  • Kao I, Drachman DB, Price DL (1976) Botulinum toxin: mechanism of presynaptic blockade. Science 193: 1256–1258

    Article  PubMed  CAS  Google Scholar 

  • Katz B (1969) The release of neural transmitter substances. Sherrington Lectures X. Liverpool University Press, Liverpool

    Google Scholar 

  • Kauffman JA, Way JF, Siegel LS, Sellin LC (1985) Comparison of the action of types A and F botulinum toxin at the rat neuromuscular junction. Toxicol Appl Pharmacol 79: 211–217

    Article  PubMed  CAS  Google Scholar 

  • Kelly RB (1993) Storage and release of neurotransmitters. Cell 72/Neuron 10 [Suppl]: 42–53

    Google Scholar 

  • Kim YI, Lömo T, Lupa MT, Thesleff S (1984) Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin. J Physiol (Lond) 356: 587–599

    CAS  Google Scholar 

  • Kriebel ME, Llados F, Matteson DR (1976) Spontaneous subminiature end-plate potentials in mouse diaphragm muscle: evidence for synchronous release. J Physiol (Lond) 262: 553–581

    CAS  Google Scholar 

  • Liley AW (1957) Spontaneous release of transmitter substance in multiquantal units. J Physiol (Lond) 136: 595–605

    CAS  Google Scholar 

  • Link E, Edelmann L, Chou JH, Binz T, Yamasaki S, Eisel U, Baumert M, Südhof TC, Niemann H, Jahn R (1992) Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis. Biochem Biophys Res Commun 189: 1017–1023

    Article  PubMed  CAS  Google Scholar 

  • Lundh H (1983) Antagonism of botulinum toxin paralysis by low temperature. Muscle Nerve 6: 56–60

    Article  PubMed  CAS  Google Scholar 

  • Lundh H, Leander S, Thesleff S (1977) Antagonism of the paralysis produced by botulinum toxin in the rat. J Neurol Sci 32: 29–43

    Article  PubMed  CAS  Google Scholar 

  • Lupa MT, Tabti N, Thesleff S, Vyskocil F, Yu SP (1986) The nature and origin of calcium-insensitive miniature end-plate potentials at rodent neuromuscular junctions. J Physiol (Lond) 381: 607–618

    CAS  Google Scholar 

  • Mallart A, Molgó J, Angaut-Petit D, Thesleff S (1989) Is the internal calcium regulation altered in type A botulinum toxin poisoned motor endings? Brain Res 479: 167–171

    Article  PubMed  CAS  Google Scholar 

  • Mellanby J, Green J (1981) How does tetanus toxin act? Neuroscience 6: 281–300

    Article  PubMed  CAS  Google Scholar 

  • Mellanby J, Thompson PA (1972) The effects of tetanus toxin at the neuromuscular junction in the goldfish. J Physiol (Lond) 224: 407–419

    CAS  Google Scholar 

  • Mellanby J, Beaumont MA, Thompson PA (1988) The effect of lanthanum on nerve terminals in goldfish muscle after paralysis with tetanus toxin. Neuroscience 25: 1095–1106

    Article  PubMed  CAS  Google Scholar 

  • Mochida S, Poulain B, Weiler U, Habermann E, Taue L (1989) Light chain of tetanus toxin intracellularly inhibits acetylcholine release at neuro-neuronal synapses, and its internalization is mediated by heavy chain. FEBS Lett 253: 47–51

    Article  PubMed  CAS  Google Scholar 

  • Molgó J, Thesleff S (1982) 4-Aminoquinoline induced “giant” miniature end-plate potentials at mammalian neuromuscular junctions. Proc R Soc Lond [Biol] 214: 229–247

    Article  Google Scholar 

  • Molgó J, Thesleff S (1984) Studies on the mode of action of botulinum toxin type A at the frog neuromuscular junction. Brain Res 296: 309–316

    Article  Google Scholar 

  • Molgó J, Lundh H, Thesleff S (1980) Potency of 3,4-diaminopyridine and 4-aminopyridine on mammalian neuromuscular transmission and the effects of pH changes. Eur J Pharmacol 61: 25–34

    Article  PubMed  Google Scholar 

  • Molgó J, Siegel LS, Tabti N, Thesleff S (1989a) A study of synchronization of quantal transmitter release from mammalian motor endings by the use of botulinal toxins type A and D. J Physiol (Lond) 411: 195–205

    Google Scholar 

  • Molgó J, DasGupta BR, Thesleff S (1989b) Characterization of the actions of botulinum neurotoxin type E at the rat neuromuscular junction. Acta Physiol Scand 137: 497–501

    Article  PubMed  Google Scholar 

  • Molgó J, Cornelia JX, Angaut-Petit D, Pécot-Dechavassine M, Tabti N, Faille L, Mallart A, Thesleff S (1990) Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions. J Physiol (Paris) 84: 152–166

    Google Scholar 

  • Neale EA, Habig WH, Schrier BK, Bergey GK, Bowers LM, Koh J (1989) Applications of tetanus toxin for structure-function studies in neuronal cell cultures. In: Nisticò G, Bizzini B, Bytchenko B, Triau R (eds) 8th international conference on tetanus. Pythagora, Rome pp 58–65

    Google Scholar 

  • Niemann H (1991) Molecular biology of clostridial neurotoxins. In: Alouf JE, Freer JH (eds) Sourcebook of bacterial protein toxins. Academic, San Diego, pp 303–348

    Google Scholar 

  • Niemann H, Blasi J, Jahn R (1994) Clostridial neurotoxins: new tools for dissecting exocytosis. Trends Cell Biol 4: 179–185

    Article  PubMed  CAS  Google Scholar 

  • Pécot-Dechavassine M, Molgó J, Thesleff S (1991) Ultrastructure of botulinum type-A poisoned frog motor nerve terminals after enhanced quantal transmitter release caused by carbonyl cyanide m-chlorophenylhydrazone. Neurosci Lett 130: 5–8

    Article  PubMed  Google Scholar 

  • Poulain B, Molgó J (1992) Botulinal neurotoxins: mode of action on neurotransmitter release. In: Conn PM (ed) Methods in neuroscience: neurotoxins, vol 8. Academic, San Diego, pp 38–54

    Google Scholar 

  • Poulain B, Tauc L, Maisey EA, Wadsworth JDF, Mohan PM, Dolly JO (1988) Neurotransmitter release is blocked intracellularly by botulinum neurotoxin, and this requires uptake of both toxin polypeptides by a process mediated by the larger chain. Proc Natl Acad Sci USA 85: 4090–4094

    Article  PubMed  CAS  Google Scholar 

  • Poulain B, Weiler U, Binz T, Niemann H, de Paiva A, Dolly JO, Leprince C, Taue, L (1993a) Functional roles of domains of Clostridial neurotoxins: the contribution from studies on Aplysia. In: DasGupta BR (ed) Botulinum and tetanus neurotoxins: neurotransmission and biochemical aspects. Plenum, New York, pp 345–360

    Google Scholar 

  • Poulain B, Rossetto O, Deloye F, Schiavo G, Taue L, Montecucco C (1993b) Antibodies against rat brain VAMP/synaptobrevin prevent inhibition of acetylcholine release by tetanus toxin or botulinum neurotoxin type B. J Neurochem 61: 1175–1178

    Article  PubMed  CAS  Google Scholar 

  • Schiavo G, Poulain B, Rossetto O, Benfenati F, Taue L, Montecucco C (1992a) Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc. EMBO J 11: 3577–3583

    PubMed  CAS  Google Scholar 

  • Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C (1992b) Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359: 832–835

    Article  PubMed  CAS  Google Scholar 

  • Schiavo G, Shone CC, Rossetto O, Alexander FCG, Montecucco C (1993a) Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin. J Biol Chem 268: 11516–11519

    PubMed  CAS  Google Scholar 

  • Schiavo G, Rossetto O, Catsicas S, Polverino de Laureto P, DasGupta BR, Benfenati F, Montecucco C (1993b) Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E. J Biol Chem 268: 23784–23787

    PubMed  CAS  Google Scholar 

  • Schiavo G, Santucci A, DasGupta BR, Metha PP, Jontes J, Benfenati F, Wilson MC, Montecucco C (1993c) Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds. FEBS Lett, 335: 99–103

    Article  PubMed  CAS  Google Scholar 

  • Schiavo G, Malizio C, Trimble WS, Polverino de Laureto P, Milan G, Sugiyama H, Johnson EA, Montecucco C (1994) Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala/Ala peptide bond. J Biol Chem 269: 20213–20216

    PubMed  CAS  Google Scholar 

  • Sellin LC (1987) Botulinum toxin and the blockade of transmitter release. Asia Pac J Pharmacol 2: 203–222

    CAS  Google Scholar 

  • Sellin LC, Thesleff S, DasGupta BR (1983) Different effects of types A and B botulinum toxin on transmitter release at the neuromuscular junction. Acta Physiol Scand 119: 127–133

    Article  PubMed  CAS  Google Scholar 

  • Simpson LL (1986) Molecular pharmacology of botulinum toxin and tetanus toxin. Annu Rev Pharmacol Toxicol 26: 427–453

    Article  PubMed  CAS  Google Scholar 

  • Simpson LL, Coffield JA, Bakry N (1993) Chelation of zinc antagonizes the neuromuscular blocking properties of the seven serotypes of botulinum neurotoxin as well as tetanus toxin. J Pharmacol Exp Ther 267: 720–727

    PubMed  CAS  Google Scholar 

  • Söllner T, Bennett MK, Whitehead SW, Scheller RH, Rothman JE (1993) A protein assembly-diassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation and fusion. Cell 75: 409–418

    Article  PubMed  Google Scholar 

  • Thesleff S (1986) Different kinds of acetylcholine release from the motor nerve. Int Rev Neurobiol 28: 59–88

    Article  PubMed  CAS  Google Scholar 

  • Thesleff S, Molgó J, Lundh H (1983) Botulinum toxin and 4-aminoquinoline induce a similar abnormal type of spontaneous quantal transmitter release at the rat neuromuscular junction. Brain Res 264: 89–97

    Article  PubMed  CAS  Google Scholar 

  • Thesleff S, Molgó J, Tågerud S (1990) Trophic interrelations at the neuromuscular junction as revealed by the use of botulinal neurotoxins. J Physiol (Paris) 84: 167–173

    CAS  Google Scholar 

  • Van der Kloot W (1989) Statistical and graphical methods for testing the hypothesis that quanta are made up of subunits. J Neurosci Methods 27: 81–89

    Article  PubMed  Google Scholar 

  • Wellhöner HH (1992) Tetanus and botulinum neurotoxins. In: Herken H, Hucho F (eds) Selective neurotoxicity. Springer, Berlin Heidelberg New York, pp 357–417 (Handbook of experimental pharmacology, vol 102)

    Google Scholar 

  • Yamasaki S, Binz T, Hayashi T, Szabo E, Yamasaki N, Eklund M, Jahn R, Niemann H (1994) Botulinum type G peoteolyses Ala81-Ala82 bond of rat synaptobrevin 2. Biochem Biophys Res Commun 200: 829–835

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Neurobiologie Cellulaire et Moléculaire, Centre National de la Recherche Scientifique, 91198, Gif sur Yvette cedex, France

    B. Poulain & J. Molgó

  2. Department of Pharmacology, University of Lund, Solvegatan 10, 223 62, Lund, Sweden

    S. Thesleff

Authors
  1. B. Poulain
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  2. J. Molgó
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  3. S. Thesleff
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Editors and Affiliations

  1. Dipartimento di Scienze Biomediche Sperimentali, Università degli Studi di Padova, Via Trieste, 75, 35121, Padova, Italia

    Cesare Montecucco

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Poulain, B., Molgó, J., Thesleff, S. (1995). Quantal Neurotransmitter Release and the Clostridial Neurotoxins’ Targets. In: Montecucco, C. (eds) Clostridial Neurotoxins. Current Topics in Microbiology and Immunology, vol 195. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85173-5_11

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  • DOI: https://doi.org/10.1007/978-3-642-85173-5_11

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