scholarly journals Interaction of botulinum and tetanus toxins with the lipid bilayer surface

1988 ◽  
Vol 251 (2) ◽  
pp. 379-383 ◽  
Author(s):  
C Montecucco ◽  
G Schiavo ◽  
Z Gao ◽  
E Bauerlein ◽  
P Boquet ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Clostridium Botulinum ◽  
Membrane Surface ◽  
Light Chains ◽  
Lipid Vesicle ◽  
Clostridium Tetani ◽  
Tetanus Neurotoxin ◽  
Clostridial Neurotoxins ◽  
Zwitterionic Lipids ◽  
Botulinum Neurotoxins

The interaction of botulinum neurotoxins serotypes A, B and E (from Clostridium botulinum) and of tetanus neurotoxin (from Clostridium tetani) with the surface of liposomes made of different lipid compositions was studied by photolabelling with a radioiodinated photoactive phosphatidylethanolamine analogue [125I-dipalmitoyl (3,4-azidosalicylamido)phosphatidylethanolamine]. When the vesicles were made of negatively charged lipids (asolectin), each of these neurotoxic proteins was radioiodinated, thus providing evidence for their attachment to the membrane surface. The presence of gangliosides on liposome membranes enhanced fixation of the neurotoxic proteins to the lipid vesicle surface. Both the heavy and light chains of the clostridial neurotoxins were involved in the attachment to the lipid bilayer surface. Each of the toxins tested here attached poorly to liposomes made of zwitterionic lipids (egg phosphatidylcholine), even when polysialogangliosides were present. The data suggest that the binding of botulinum and tetanus neurotoxins to their target neuronal cells involves negatively charged lipids and polysialogangliosides on the cell membrane.

Structure and function of tetanus and botulinum neurotoxins

1995 ◽  
Vol 28 (4) ◽  
pp. 423-472 ◽  
Author(s):  
Cesare Montecucco ◽  
Giampietro Schiavo
Keyword(s):  
Coordination Mechanism ◽  
Vesicle Membrane ◽  
Peptide Bonds ◽  
Tetanus Neurotoxin ◽  
Clostridial Neurotoxins ◽  
Endopeptidase Activity ◽  
Botulinum Neurotoxins ◽  
Protein Components ◽  
And Function ◽  
Polypeptide Chains

Tetanus and botulinum neurotoxins are produced byClostridiaand cause the neuroparalytic syndromes of tetanus and botulism. Tetanus neurotoxin acts mainly at the CNS synapse, while the seven botulinum neurotoxins act peripherally. Clostridial neurotoxins share a similar mechanism of cell intoxication: they block the release of neurotransmitters. They are composed of two disulfide-linked polypeptide chains. The larger subunit is responsible for neurospecific binding and cell penetration. Reduction releases the smaller chain in the neuronal cytosol, where it displays its zinc-endopeptidase activity specific for protein components of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum neurotoxins B, D, F and G recognize specifically VAMP/synaptobrevin. This integral protein of the synaptic vesicle membrane is cleaved at single peptide bonds, which differ for each neurotoxin. Botulinum A, and E neurotoxins recognize and cleave specifically SNAP-25, a protein of the presynaptic membrane, at two different sites within the carboxyl-terminus. Botulinum neurotoxin type C cleaves syntaxin, another protein of the nerve plasmalemma. These results indicate that VAMP, SNAP-25 a n d syntaxin play a central role in neuroexocytosis. These three proteins are conserved from yeast to humans and are essential in a variety of docking and fusion events in every cell. Tetanus and botulinum neurotoxins form a new group of zinc-endopeptidases with characteristic sequence, mode of zinc coordination, mechanism of activation and target recognition. They will be of great value in the unravelling of the mechanisms of exocytosis and endocytosis, as they are in the clinical treatment of dystonias.

scholarly journals Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses

1999 ◽  
Vol 354 (1381) ◽  
pp. 259-268 ◽  
Author(s):  
Rossella Pellizzari ◽  
Ornella Rossetto ◽  
Giampietro Schiavo ◽  
Cesare Montecucco
Keyword(s):  
Membrane Protein ◽  
Neuromuscular Junction ◽  
Synaptic Vesicles ◽  
Peptide Bonds ◽  
Spastic Paralysis ◽  
Tetanus Neurotoxin ◽  
Therapeutic Uses ◽  
Clostridial Neurotoxins ◽  
Botulinum Neurotoxins ◽  
Type C

The clostridial neurotoxins responsible for tetanus and botulism are proteins consisting of three domains endowed with different functions: neurospecific binding, membrane translocation and proteolysis for specific components of the neuroexocytosis apparatus. Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction, is internalized and transported retroaxonally to the spinal cord. The spastic paralysis induced by the toxin is due to the blockade of neurotransmitter release from spinal inhibitory interneurons. In contrast, the seven serotypes of botulinum neurotoxins (BoNTs) act at the periphery by inducing a flaccid paralysis due to the inhibition of acetylcholine release at the neuromuscular junction. TeNT and BoNT serotypes B, D, F and G cleave specifically at single but different peptide bonds, of the vesicle associated membrane protein (VAMP) synaptobrevin, a membrane protein of small synaptic vesicles (SSVs). BoNT types A, C and E cleave SNAP–25 at different sites located within the carboxyl–terminus, while BoNT type C additionally cleaves syntaxin. The remarkable specificity of BoNTs is exploited in the treatment of human diseases characterized by an hyperfunction of cholinergic terminals.

scholarly journals Distribution of Clostridium botulinum and Clostridium tetani in Okinawa Prefecture

1992 ◽  
Vol 66 (12) ◽  
pp. 1639-1644 ◽  
Author(s):  
Toyoko KOBAYASHI ◽  
Kunitomo WATANABE ◽  
Kazue UENO
Keyword(s):  
Clostridium Botulinum ◽  
Clostridium Tetani ◽  
Okinawa Prefecture

Development of an in vitro cell-based bioassay for the detection of Clostridium botulinum neurotoxins by using mESC-derived neurons grown on multi electrode arrays

Toxicon ◽  
2016 ◽  
Vol 123 ◽  
pp. S44
Author(s):  
Stephen P. Jenkinson ◽  
Denis Grandgirard ◽  
Martina Heidemann ◽  
Anne Tscherter ◽  
Marc-André Avondet ◽  
...  
Keyword(s):  
Clostridium Botulinum ◽  
Electrode Arrays ◽  
Botulinum Neurotoxins

scholarly journals Clostridium botulinum in soil on the site of the former Metropolitan (Caledonian) Cattle Market, London

1979 ◽  
Vol 83 (2) ◽  
pp. 237-241 ◽  
Author(s):  
G. R. Smith ◽  
R. A. Milligan
Keyword(s):  
Small Proportion ◽  
Clostridium Botulinum ◽  
Type A ◽  
Soil Samples ◽  
Farm Animals ◽  
Clostridium Tetani ◽  
Faecal Contamination ◽  
The Many ◽  
Soil Surveys ◽  
Cattle Market

summarySixty soil samples were collected from the redeveloped site of the former Metropolitan (Caledonian) Cattle Market, Islington, London. Of these, 15 (25%) contained Clostridium botulinum and no less than four types (B, C, D and E) were demonstrated.Early British soil surveys suggested that only 4–8% of samples contained Cl. botulinum (type A or B). Although there can be no absolute proof, it seems likely that the striking prevalence at the Market site was the result of faecal contamination by a small proportion of the many millions of farm animals brought there from elsewhere.The distribution of Clostridium tetani was uneven, but of 18 soil samples taken from one area of the Market site, 16 (89%) were positive.

scholarly journals A Novel Tetanus Neurotoxin-insensitive Vesicle-associated Membrane Protein in SNARE Complexes of the Apical Plasma Membrane of Epithelial Cells

1998 ◽  
Vol 9 (6) ◽  
pp. 1437-1448 ◽  
Author(s):  
Thierry Galli ◽  
Ahmed Zahraoui ◽  
Vadakkanchery V. Vaidyanathan ◽  
Graça Raposo ◽  
Jian Min Tian ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Membrane Protein ◽  
Apical Plasma Membrane ◽  
Domain Specific ◽  
Tetanus Neurotoxin ◽  
Synaptic Vesicle Exocytosis ◽  
Clostridial Neurotoxins ◽  
Vesicle Exocytosis ◽  
Syntaxin 3

The importance of soluble N-ethyl maleimide (NEM)-sensitive fusion protein (NSF) attachment protein (SNAP) receptors (SNAREs) in synaptic vesicle exocytosis is well established because it has been demonstrated that clostridial neurotoxins (NTs) proteolyze the vesicle SNAREs (v-SNAREs) vesicle-associated membrane protein (VAMP)/brevins and their partners, the target SNAREs (t-SNAREs) syntaxin 1 and SNAP25. Yet, several exocytotic events, including apical exocytosis in epithelial cells, are insensitive to numerous clostridial NTs, suggesting the presence of SNARE-independent mechanisms of exocytosis. In this study we found that syntaxin 3, SNAP23, and a newly identified VAMP/brevin, tetanus neurotoxin (TeNT)-insensitive VAMP (TI-VAMP), are insensitive to clostridial NTs. In epithelial cells, TI-VAMP–containing vesicles were concentrated in the apical domain, and the protein was detected at the apical plasma membrane by immunogold labeling on ultrathin cryosections. Syntaxin 3 and SNAP23 were codistributed at the apical plasma membrane where they formed NEM-dependent SNARE complexes with TI-VAMP and cellubrevin. We suggest that TI-VAMP, SNAP23, and syntaxin 3 can participate in exocytotic processes at the apical plasma membrane of epithelial cells and, more generally, domain-specific exocytosis in clostridial NT-resistant pathways.

scholarly journals Norepinephrine exocytosis stimulated by α–latrotoxin requires both external and stored Ca 2+ and is mediated by latrophilin, G proteins and phospholipase C

1999 ◽  
Vol 354 (1381) ◽  
pp. 379-386 ◽  
Author(s):  
M. Atiqur Rahman ◽  
Anthony C. Ashton ◽  
Frédéric A. Meunier ◽  
Bazbek A. Davletov ◽  
J. Oliver Dolly ◽  
...  
Keyword(s):  
Phospholipase C ◽  
G Protein ◽  
G Proteins ◽  
Fluorescent Dyes ◽  
Transmembrane Protein ◽  
Clostridial Neurotoxins ◽  
Dependent Component ◽  
Intracellular Ca ◽  
Botulinum Neurotoxins ◽  
Vesicular Exocytosis

α–latrotoxin (LTX) stimulates massive release of neurotransmitters by binding to a heptahelical transmembrane protein, latrophilin. Our experiments demonstrate that latrophilin is a G–protein–coupled receptor that specifically associates with heterotrimeric G proteins. The latrophilin–G protein complex is very stable in the presence of GDP but dissociates when incubated with GTP, suggesting a functional interaction. As revealed by immunostaining, latrophilin interacts with Gα q/11 and Gα o but not with Gα s , Gα i or Gα z , indicating that this receptor may couple to several G proteins but it is not promiscuous. The mechanisms underlying LTX–evoked norepinephrine secretion from rat brain nerve terminals were also studied. In the presence of extracellular Ca 2+ , LTX triggers vesicular exocytosis because botulinum neurotoxins E, C1 or tetanus toxin inhibit the Ca 2+ –dependent component of the toxin–evoked release. Based on (i) the known involvement of Gα q in the regulation of inositol–1,4,5–triphosphate generation and (ii) the requirement of Ca 2+ in LTX action, we tested the effect of inhibitors of Ca 2+ mobilization on the toxin–evoked norepinephrine release. It was found that aminosteroid U73122, which inhibits the coupling of G proteins to phospholipase C, blocks the Ca 2+ –dependent toxin's action. Thapsigargin, which depletes intracellular Ca 2+ stores, also potently decreases the effect of LTX in the presence of extracellular Ca 2+ . On the other hand, clostridial neurotoxins or drugs interfering with Ca 2+ metabolism do not inhibit the Ca 2+ –independent component of LTX–stimulated release. In the absence of Ca 2+ , the toxin induces in the presynaptic membrane non–selective pores permeable to small fluorescent dyes; these pores may allow efflux of neurotransmitters from the cytoplasm. Our results suggest that LTX stimulates norepinephrine exocytosis only in the presence of external Ca 2+ provided intracellular Ca 2+ stores are unperturbed and that latrophilin, G proteins and phospholipase C may mediate the mobilization of stored Ca 2+ , which then triggers secretion.

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