Neurotoxicity of clostridium toxins (Homo sapiens)
From WikiPathways
Description
Strains of Clostridium botulinum produce seven serologically distinct toxins, BoNT/A, B, C, D, E, F, and G. An eighth toxin, BoNT/H has recently been identified (Barash & Arnon 2014) but its molecular properties have not yet been described. Human poisoning most commonly result from ingestion of toxin contaminated food. More rarely, it is due to wound infection or clostridial colonization of the gut of an infant whose own gut flora have not yet developed or of an older individual whose flora have been suppressed. While all seven characterized toxins can cleave human target proteins, three, BoNT/A, B, and E, are most commonly associated with human disease (Hatheway 1995; Sakaguchi 1982). BoNT/F is also able to cause human botulism.<p>Once ingested, the botulinum toxin must be taken up from the gut lumen into the circulation, a process mediated by four accessory proteins. These proteins form a complex that mediates transcytosis of the toxin molecule across the gut epithelium, allowing its entry into the circulation. The accessory proteins produced by different C. botulinum strains differ in their affinities for polarized epithelia of different species (e.g., human versus canine), and may thus be a key factor in human susceptibility to the toxins of strains A, B, and E and resistance to the others (Simpson 2004).<p>Clostridium tetani produces TeNT toxin. Human poisoning is the result of toxin secretion by bacteria growing in an infected wound and the toxin is released directly into the circulation.<p>Circulating clostridial toxins are taken up by neurons at neuromuscular junctions. They bind to specific gangliosides (BoNT/C, TeNT) or to both gangliosides and synaptic vesicle proteins (BoNT/A, B, D G) exposed on the neuronal plasma membrane during vesicle exocytosis (Montal 2010). All seven characterized forms of BoNT are thought to be taken up into synaptic vesicles as these re-form at the neuromuscular junction. These vesicles remain close to the site of uptake and are rapidly re-loaded with neurotransmitter and acidified (Sudhoff 2004). TeNT, in contrast, is taken up into clathrin coated vesicles that reach the neuron cell body by retrograde transport and then possibly other neurons before undergoing acidification. Vesicle acidification causes a conformational change in the toxin, allowing its HC part to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved and the cytosolic LC functions as a zinc metalloprotease to cleave specific bonds in proteins on the cytosolic faces of synaptic vesicles and plasma membranes that normally mediate exocytosis (Lalli et al. 2003; Montal 2010). Source:Reactome.</div>
Quality Tags
Ontology Terms
Bibliography
View all... |
- Montal M.; ''Botulinum neurotoxin: a marvel of protein design.''; PubMed Europe PMC Scholia
- Dasgupta BR, Datta A.; ''Botulinum neurotoxin type B (strain 657): partial sequence and similarity with tetanus toxin.''; PubMed Europe PMC Scholia
- Giménez JA, DasGupta BR.; ''Botulinum neurotoxin type E fragmented with endoproteinase Lys-C reveals the site trypsin nicks and homology with tetanus neurotoxin.''; PubMed Europe PMC Scholia
- Foran P, Shone CC, Dolly JO.; ''Differences in the protease activities of tetanus and botulinum B toxins revealed by the cleavage of vesicle-associated membrane protein and various sized fragments.''; PubMed Europe PMC Scholia
- Schiavo G, Santucci A, Dasgupta BR, Mehta PP, Jontes J, Benfenati F, Wilson MC, Montecucco C.; ''Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds.''; PubMed Europe PMC Scholia
- Binz T, Blasi J, Yamasaki S, Baumeister A, Link E, Südhof TC, Jahn R, Niemann H.; ''Proteolysis of SNAP-25 by types E and A botulinal neurotoxins.''; PubMed Europe PMC Scholia
- Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, Chapman ER.; ''SV2 is the protein receptor for botulinum neurotoxin A.''; PubMed Europe PMC Scholia
- Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C.; ''Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.''; PubMed Europe PMC Scholia
- Krieglstein K, Henschen A, Weller U, Habermann E.; ''Arrangement of disulfide bridges and positions of sulfhydryl groups in tetanus toxin.''; PubMed Europe PMC Scholia
- Rummel A, Häfner K, Mahrhold S, Darashchonak N, Holt M, Jahn R, Beermann S, Karnath T, Bigalke H, Binz T.; ''Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding site prior to stimulation-dependent uptake with botulinum neurotoxin F utilising the three isoforms of SV2 as second receptor.''; PubMed Europe PMC Scholia
- Hatheway CL.; ''Botulism: the present status of the disease.''; PubMed Europe PMC Scholia
- Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC.; ''Crystal structure of botulinum neurotoxin type A and implications for toxicity.''; PubMed Europe PMC Scholia
- Schiavo G, Rossetto O, Catsicas S, Polverino de Laureto P, DasGupta BR, Benfenati F, Montecucco C.; ''Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E.''; PubMed Europe PMC Scholia
- Yamasaki S, Binz T, Hayashi T, Szabo E, Yamasaki N, Eklund M, Jahn R, Niemann H.; ''Botulinum neurotoxin type G proteolyses the Ala81-Ala82 bond of rat synaptobrevin 2.''; PubMed Europe PMC Scholia
- Montecucco C, Schiavo G.; ''Mechanism of action of tetanus and botulinum neurotoxins.''; PubMed Europe PMC Scholia
- Lalli G, Bohnert S, Deinhardt K, Verastegui C, Schiavo G.; ''The journey of tetanus and botulinum neurotoxins in neurons.''; PubMed Europe PMC Scholia
- Link E, Edelmann L, Chou JH, Binz T, Yamasaki S, Eisel U, Baumert M, Südhof TC, Niemann H, Jahn R.; ''Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis.''; PubMed Europe PMC Scholia
- Karalewitz AP, Fu Z, Baldwin MR, Kim JJ, Barbieri JT.; ''Botulinum neurotoxin serotype C associates with dual ganglioside receptors to facilitate cell entry.''; PubMed Europe PMC Scholia
- Simpson LL.; ''Identification of the major steps in botulinum toxin action.''; PubMed Europe PMC Scholia
- Sun S, Suresh S, Liu H, Tepp WH, Johnson EA, Edwardson JM, Chapman ER.; ''Receptor binding enables botulinum neurotoxin B to sense low pH for translocation channel assembly.''; PubMed Europe PMC Scholia
- Barash JR, Arnon SS.; ''A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins.''; PubMed Europe PMC Scholia
- Chen C, Fu Z, Kim JJ, Barbieri JT, Baldwin MR.; ''Gangliosides as high affinity receptors for tetanus neurotoxin.''; PubMed Europe PMC Scholia
- Kumaran D, Eswaramoorthy S, Furey W, Navaza J, Sax M, Swaminathan S.; ''Domain organization in Clostridium botulinum neurotoxin type E is unique: its implication in faster translocation.''; PubMed Europe PMC Scholia
- Schiavo G, Poulain B, Rossetto O, Benfenati F, Tauc L, Montecucco C.; ''Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc.''; PubMed Europe PMC Scholia
- Peng L, Tepp WH, Johnson EA, Dong M.; ''Botulinum neurotoxin D uses synaptic vesicle protein SV2 and gangliosides as receptors.''; PubMed Europe PMC Scholia
- Dong M, Richards DA, Goodnough MC, Tepp WH, Johnson EA, Chapman ER.; ''Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells.''; PubMed Europe PMC Scholia
- Sun S, Tepp WH, Johnson EA, Chapman ER.; ''Botulinum neurotoxins B and E translocate at different rates and exhibit divergent responses to GT1b and low pH.''; PubMed Europe PMC Scholia
- Kroken AR, Karalewitz AP, Fu Z, Kim JJ, Barbieri JT.; ''Novel ganglioside-mediated entry of botulinum neurotoxin serotype D into neurons.''; PubMed Europe PMC Scholia
- Lee K, Gu S, Jin L, Le TT, Cheng LW, Strotmeier J, Kruel AM, Yao G, Perry K, Rummel A, Jin R.; ''Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity.''; PubMed Europe PMC Scholia
- Amatsu S, Sugawara Y, Matsumura T, Kitadokoro K, Fujinaga Y.; ''Crystal structure of Clostridium botulinum whole hemagglutinin reveals a huge triskelion-shaped molecular complex.''; PubMed Europe PMC Scholia
- Fu Z, Chen C, Barbieri JT, Kim JJ, Baldwin MR.; ''Glycosylated SV2 and gangliosides as dual receptors for botulinum neurotoxin serotype F.''; PubMed Europe PMC Scholia
- Südhof TC, De Camilli P, Niemann H, Jahn R.; ''Membrane fusion machinery: insights from synaptic proteins.''; PubMed Europe PMC Scholia
- Mochida S, Poulain B, Weller U, Habermann E, Tauc L.; ''Light chain of tetanus toxin intracellularly inhibits acetylcholine release at neuro-neuronal synapses, and its internalization is mediated by heavy chain.''; PubMed Europe PMC Scholia
- Sakaguchi G.; ''Clostridium botulinum toxins.''; PubMed Europe PMC Scholia
- Swaminathan S, Eswaramoorthy S.; ''Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B.''; PubMed Europe PMC Scholia
- Arndt JW, Chai Q, Christian T, Stevens RC.; ''Structure of botulinum neurotoxin type D light chain at 1.65 A resolution: repercussions for VAMP-2 substrate specificity.''; PubMed Europe PMC Scholia
- Willjes G, Mahrhold S, Strotmeier J, Eichner T, Rummel A, Binz T.; ''Botulinum neurotoxin G binds synaptotagmin-II in a mode similar to that of serotype B: tyrosine 1186 and lysine 1191 cause its lower affinity.''; PubMed Europe PMC Scholia
- Blasi J, Chapman ER, Yamasaki S, Binz T, Niemann H, Jahn R.; ''Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin.''; PubMed Europe PMC Scholia
- Kozaki S, Kamata Y, Watarai S, Nishiki T, Mochida S.; ''Ganglioside GT1b as a complementary receptor component for Clostridium botulinum neurotoxins.''; PubMed Europe PMC Scholia
- Peng L, Berntsson RP, Tepp WH, Pitkin RM, Johnson EA, Stenmark P, Dong M.; ''Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins.''; PubMed Europe PMC Scholia
- Deinhardt K, Berninghausen O, Willison HJ, Hopkins CR, Schiavo G.; ''Tetanus toxin is internalized by a sequential clathrin-dependent mechanism initiated within lipid microdomains and independent of epsin1.''; PubMed Europe PMC Scholia
- Schiavo G, Malizio C, Trimble WS, Polverino de Laureto P, Milan G, Sugiyama H, Johnson EA, Montecucco C.; ''Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond.''; PubMed Europe PMC Scholia
- Dong M, Liu H, Tepp WH, Johnson EA, Janz R, Chapman ER.; ''Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons.''; PubMed Europe PMC Scholia
- Agarwal R, Eswaramoorthy S, Kumaran D, Binz T, Swaminathan S.; ''Structural analysis of botulinum neurotoxin type E catalytic domain and its mutant Glu212-->Gln reveals the pivotal role of the Glu212 carboxylate in the catalytic pathway.''; PubMed Europe PMC Scholia
- Schmidt JJ, Sathyamoorthy V, DasGupta BR.; ''Partial amino acid sequence of the heavy and light chains of botulinum neurotoxin type A.''; PubMed Europe PMC Scholia
- Turton K, Chaddock JA, Acharya KR.; ''Botulinum and tetanus neurotoxins: structure, function and therapeutic utility.''; PubMed Europe PMC Scholia
- Koriazova LK, Montal M.; ''Translocation of botulinum neurotoxin light chain protease through the heavy chain channel.''; PubMed Europe PMC Scholia
- Vaidyanathan VV, Yoshino K, Jahnz M, Dörries C, Bade S, Nauenburg S, Niemann H, Binz T.; ''Proteolysis of SNAP-25 isoforms by botulinum neurotoxin types A, C, and E: domains and amino acid residues controlling the formation of enzyme-substrate complexes and cleavage.''; PubMed Europe PMC Scholia
- Benefield DA, Dessain SK, Shine N, Ohi MD, Lacy DB.; ''Molecular assembly of botulinum neurotoxin progenitor complexes.''; PubMed Europe PMC Scholia
- Fujinaga Y, Sugawara Y, Matsumura T.; ''Uptake of botulinum neurotoxin in the intestine.''; PubMed Europe PMC Scholia
- Yamasaki S, Baumeister A, Binz T, Blasi J, Link E, Cornille F, Roques B, Fykse EM, Südhof TC, Jahn R.; ''Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin.''; PubMed Europe PMC Scholia
- Sathyamoorthy V, Dasgupta BR, Foley J, Niece RL.; ''Botulinum neurotoxin type A: cleavage of the heavy chain into two halves and their partial sequences.''; PubMed Europe PMC Scholia
- Henderson I, Whelan SM, Davis TO, Minton NP.; ''Genetic characterisation of the botulinum toxin complex of Clostridium botulinum strain NCTC 2916.''; PubMed Europe PMC Scholia
- Foran P, Lawrence GW, Shone CC, Foster KA, Dolly JO.; ''Botulinum neurotoxin C1 cleaves both syntaxin and SNAP-25 in intact and permeabilized chromaffin cells: correlation with its blockade of catecholamine release.''; PubMed Europe PMC Scholia
- Sudhof TC.; ''The synaptic vesicle cycle.''; PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
View all... |