bungarotoxins

Summary

Summary: Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms.

Top Publications

  1. Sampaio L, Hamassaki Britto D, Markus R. Influence of melatonin on the development of functional nicotinic acetylcholine receptors in cultured chick retinal cells. Braz J Med Biol Res. 2005;38:603-13 pubmed
    ..This common pattern of action on different cell models that express alpha-bungarotoxin-sensitive receptors probably reflects a more general mechanism of regulation of these receptors. ..
  2. Yanoshita R, Ogawa Y, Murayama N, Omori Satoh T, Saguchi K, Higuchi S, et al. Molecular cloning of the major lethal toxins from two kraits (Bungarus flaviceps and Bungarus candidus). Toxicon. 2006;47:416-24 pubmed
    ..and enzymatically digested peptides revealed that the A and B chains were highly homologous to those of beta-bungarotoxins (beta-Bgts) from Bungarus multicinctus, respectively...
  3. Baier C, Barrantes F. Sphingolipids are necessary for nicotinic acetylcholine receptor export in the early secretory pathway. J Neurochem. 2007;101:1072-84 pubmed
    ..On the basis of these effects we propose a 'chaperone-like' SL intervention at early stages of the AChR biosynthetic pathway, affecting both the efficiency of the assembly process and subsequent receptor trafficking to the cell surface. ..
  4. Dellis O, Dedos S, Tovey S, Taufiq Ur Rahman -, Dubel S, Taylor C. Ca2+ entry through plasma membrane IP3 receptors. Science. 2006;313:229-33 pubmed
    ..IP(3)Rs are unusual among endoplasmic reticulum proteins in being also functionally expressed at the PM, where very few IP3Rs contribute substantially to the Ca2+ entry evoked by the BCR. ..
  5. Williams M, Burton B, Urrutia A, Shcherbatko A, Chavez Noriega L, Cohen C, et al. Ric-3 promotes functional expression of the nicotinic acetylcholine receptor alpha7 subunit in mammalian cells. J Biol Chem. 2005;280:1257-63 pubmed
    ..Thus, ric-3 appears to be necessary for proper folding and/or assembly of alpha7 receptors in HEK293 cells. ..
  6. Sekine Aizawa Y, Huganir R. Imaging of receptor trafficking by using alpha-bungarotoxin-binding-site-tagged receptors. Proc Natl Acad Sci U S A. 2004;101:17114-9 pubmed
    ..The BBS tag is a flexible approach for labeling membrane proteins and studying their dynamic trafficking. ..
  7. Chen Y. Phospholipase A(2) activity of beta-bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons. J Neurobiol. 2005;64:213-23 pubmed
    ..It is proposed that the CGNs can be a useful tool for studying interactions of the molecules on neuronal plasma membrane with beta-BuTX that mediates the specific cytotoxicity. ..
  8. Lin W, Dominguez B, Yang J, Aryal P, Brandon E, Gage F, et al. Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism. Neuron. 2005;46:569-79 pubmed
    ..Genetic elimination of Cdk5 or blocking ACh production prevents the dispersion of AChR clusters in agrin mutants. Therefore, we propose that ACh negatively regulates neuromuscular synapse formation through a Cdk5-dependent mechanism. ..
  9. Sadasivam G, Willmann R, Lin S, Erb Vögtli S, Kong X, Ruegg M, et al. Src-family kinases stabilize the neuromuscular synapse in vivo via protein interactions, phosphorylation, and cytoskeletal linkage of acetylcholine receptors. J Neurosci. 2005;25:10479-93 pubmed
    ..SFKs hold the postsynaptic apparatus together through stabilization of AChR-rapsyn interaction and AChR phosphorylation. In addition, SFKs control rapsyn levels and AChR-cytoskeletal linkage. ..

More Information

Publications62

  1. Guo J, Chen H, Puhl H, Ikeda S. Fluorophore-assisted light inactivation produces both targeted and collateral effects on N-type calcium channel modulation in rat sympathetic neurons. J Physiol. 2006;576:477-92 pubmed
    ..These data challenge the assumption that the fluorophore-tagged protein is the sole target of FALI and provide evidence that collateral damage to proximal proteins occurs following fluorophore illumination. ..
  2. Moser N, Mechawar N, Jones I, Gochberg Sarver A, Orr Urtreger A, Plomann M, et al. Evaluating the suitability of nicotinic acetylcholine receptor antibodies for standard immunodetection procedures. J Neurochem. 2007;102:479-92 pubmed
    ..Thus, particular caution should be exerted with regards to the experimental approach used to visualize nicotinic acetylcholine receptors in the brain. ..
  3. Cheng Y, Wang J, Chang L. B chain is a functional subunit of beta-bungarotoxin for inducing apoptotic death of human neuroblastoma SK-N-SH cells. Toxicon. 2008;51:304-15 pubmed
    ..Taken together, our data indicate that B chain is a functional subunit responsible for the cytotoxicity of beta-Bgt, and suggest that the cytotoxicity of beta-Bgt is mediated by NMDA receptor and potassium conductance. ..
  4. Yampolsky P, Gensler S, McArdle J, Witzemann V. AChR channel conversion and AChR-adjusted neuronal survival during embryonic development. Mol Cell Neurosci. 2008;37:634-45 pubmed publisher
  5. Chang L, Wang J, Cheng Y, Chou W. Genetic organization of Bungarus multicinctus protease inhibitor-like proteins. Toxicon. 2008;51:1490-5 pubmed publisher
  6. Bal R, Erdogan S, Theophilidis G, Baydas G, Naziroglu M. Assessing the effects of the neonicotinoid insecticide imidacloprid in the cholinergic synapses of the stellate cells of the mouse cochlear nucleus using whole-cell patch-clamp recording. Neurotoxicology. 2010;31:113-20 pubmed publisher
    ..3+/-3.4 pA inward current (n=4). We conclude that exposure to IMI at concentrations >or=10 microM for <1 min can change the membrane properties of neurons that have nAChRs and, as a consequence, their function...
  7. Murakami M, Kini R, Arni R. Crystal structure of bucain, a three-fingered toxin from the venom of the Malayan krait (Bungarus candidus). Protein Pept Lett. 2009;16:1473-7 pubmed
    ..10 A resolution and based on the molecular topology and hydrophobicity profile is structurally classified as a three-fingered alpha-neurotoxin possessing a positively charged AChR-binding site...
  8. Huang L, Abbott L, Winzer Serhan U. Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum. Neuroscience. 2007;146:1854-68 pubmed
  9. Leeprasert W, Kaojarern S. Specific antivenom for Bungarus candidus. J Med Assoc Thai. 2007;90:1467-76 pubmed
    ..The present article is the first report on the clinical response to the specific antivenom for Bungarus candidus...
  10. Gotti C, Clementi F. Neuronal nicotinic receptors: from structure to pathology. Prog Neurobiol. 2004;74:363-96 pubmed
    ..Finally, the role of NAChRs in disease will be considered in some details. ..
  11. Cheng Y, Chen K, Lin S, Chang L. Divergence of genes encoding B chains of beta-bungarotoxins. Toxicon. 2006;47:322-9 pubmed
    The structural organization of the genes encoding B2, B4, B5 and B6 chains of beta-bungarotoxins are reported in this study...
  12. McIntosh J, Plazas P, Watkins M, Gómez Casati M, Olivera B, Elgoyhen A. A novel alpha-conotoxin, PeIA, cloned from Conus pergrandis, discriminates between rat alpha9alpha10 and alpha7 nicotinic cholinergic receptors. J Biol Chem. 2005;280:30107-12 pubmed
    ..Alpha-conotoxin PeIA represents a novel probe to differentiate responses mediated either through alpha9alpha10 or alpha7 nAChRs in those tissues where both receptors are expressed. ..
  13. Kumari S, Borroni V, Chaudhry A, Chanda B, Massol R, Mayor S, et al. Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway. J Cell Biol. 2008;181:1179-93 pubmed publisher
    ..This pathway may regulate AChR levels at ligand-gated synapses and in pathological conditions such as the autoimmune disease myasthenia gravis. ..
  14. Doley R, Kini R. Protein complexes in snake venom. Cell Mol Life Sci. 2009;66:2851-71 pubmed publisher
    ..Here, we describe the structure and function of various protein complexes of snake venoms and their role in snake venom toxicity. ..
  15. Wu P, Ma D, Pierzchala M, Wu J, Yang L, Mai X, et al. The Drosophila acetylcholine receptor subunit D alpha5 is part of an alpha-bungarotoxin binding acetylcholine receptor. J Biol Chem. 2005;280:20987-94 pubmed
    ..A peptide-specific antibody raised against the D alpha5 subunit provides further evidence that this subunit is a component of an alpha-bungarotoxin binding nicotinic acetylcholine receptor from the central nervous system of Drosophila. ..
  16. Cheng Y, Yan F, Chang L. Taiwan cobra chymotrypsin inhibitor: cloning, functional expression and gene organization. Biochim Biophys Acta. 2005;1747:213-20 pubmed
    ..atra chymotrypsin inhibitor and beta-bungarotoxin B1 chain genes was up to 83%. These findings strongly suggest that snake Kunitz/BPTI protease inhibitors and neurotoxic homologs may have originated from a common ancestor...
  17. Drisdel R, Manzana E, Green W. The role of palmitoylation in functional expression of nicotinic alpha7 receptors. J Neurosci. 2004;24:10502-10 pubmed
    ..In conclusion, our data indicate a function for protein palmitoylation in which palmitoylation of assembling alpha7 subunits in the ER has a role in the formation of functional BgtRs. ..
  18. Borroni V, Baier C, Lang T, Bonini I, White M, Garbus I, et al. Cholesterol depletion activates rapid internalization of submicron-sized acetylcholine receptor domains at the cell membrane. Mol Membr Biol. 2007;24:1-15 pubmed
  19. Park H, Lee P, Ahn Y, Choi Y, Lee G, Lee D, et al. Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action. Eur J Neurosci. 2007;26:79-89 pubmed
    ..Along with various neuroprotective effects of nicotine, the anti-inflammatory mechanism of nicotine could have a major therapeutic implication in the preventive treatment of PD. ..
  20. Dellisanti C, Yao Y, Stroud J, Wang Z, Chen L. Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution. Nat Neurosci. 2007;10:953-62 pubmed
    ..Our structural and functional studies show essential features of the nAChR and provide new insights into the gating mechanism. ..
  21. Kasheverov I, Zhmak M, Fish A, Rucktooa P, Khruschov A, Osipov A, et al. Interaction of alpha-conotoxin ImII and its analogs with nicotinic receptors and acetylcholine-binding proteins: additional binding sites on Torpedo receptor. J Neurochem. 2009;111:934-44 pubmed publisher
  22. Zhu D, Xiong W, Mei L. Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering. J Neurosci. 2006;26:4841-51 pubmed
    ..These results provide insight into mechanisms of AChR cluster formation. ..
  23. Bruneau E, Sutter D, Hume R, Akaaboune M. Identification of nicotinic acetylcholine receptor recycling and its role in maintaining receptor density at the neuromuscular junction in vivo. J Neurosci. 2005;25:9949-59 pubmed
    ..These results identify an activity-dependent AChR-recycling mechanism that enables the regulation of receptor density, which could lead to rapid alterations in synaptic efficacy. ..
  24. Wu P, Chang L, Kao Y, Wang K. Beta-Bungarotoxin induction of neurite outgrowth in NB41A3 cells. Toxicon. 2008;52:354-60 pubmed publisher
    ..Taken together, our results suggest the beta-Bgt-induced outgrowth of neurite from NB41A3 cells may be mediated by small G proteins. ..
  25. Tseng W, Lin Shiau S. Calcium-activated NO production plays a role in neuronal death induced by beta-bungarotoxin in primary cultures of cerebellar granular neurons. Naunyn Schmiedebergs Arch Pharmacol. 2003;367:451-61 pubmed
    ..This potent neurotoxin will be a useful tool for studying neurotoxic processes and using this model system will allow us to find neuroprotective agents. ..
  26. Zhao L, Kuo Y, George A, Peng J, Purandare M, Schroeder K, et al. Functional properties of homomeric, human alpha 7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 human epithelial cell line. J Pharmacol Exp Ther. 2003;305:1132-41 pubmed
  27. Wang H, Yu M, Ochani M, Amella C, Tanovic M, Susarla S, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003;421:384-8 pubmed
    ..Thus, the nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway. ..
  28. Lansdell S, Millar N. Molecular characterization of Dalpha6 and Dalpha7 nicotinic acetylcholine receptor subunits from Drosophila: formation of a high-affinity alpha-bungarotoxin binding site revealed by expression of subunit chimeras. J Neurochem. 2004;90:479-89 pubmed
    ..In addition to the formation of homomeric nAChR complexes, evidence has been obtained from both radioligand binding and co-immunoprecipitation studies for the co-assembly of Dalpha6 and Dalpha7 into heteromeric cell surface complexes. ..
  29. Tseng W, Lin Shiau S. Neuronal death signaling by beta-bungarotoxin through the activation of the N-methyl-D-aspartate (NMDA) receptor and L-type calcium channel. Biochem Pharmacol. 2003;65:131-42 pubmed
    ..Therefore, we suggest that this polypeptide neurotoxin, as a result of its high potency and irreversible properties, is a useful tool to elucidate the mechanisms of neurodegenerative diseases. ..
  30. Herkert M, Shakhman O, Schweins E, Becker C. Beta-bungarotoxin is a potent inducer of apoptosis in cultured rat neurons by receptor-mediated internalization. Eur J Neurosci. 2001;14:821-8 pubmed
  31. Shakhman O, Herkert M, Rose C, Humeny A, Becker C. Induction by beta-bungarotoxin of apoptosis in cultured hippocampal neurons is mediated by Ca(2+)-dependent formation of reactive oxygen species. J Neurochem. 2003;87:598-608 pubmed
  32. Megeath L, Kirber M, Hopf C, Hoch W, Fallon J. Calcium-dependent maintenance of agrin-induced postsynaptic specializations. Neuroscience. 2003;122:659-68 pubmed
    ..These findings suggest an avenue by which postsynaptic stability can be regulated by modification of intracellular signaling pathways that are distinct from those used during synapse formation. ..
  33. Ellison M, McIntosh J, Olivera B. Alpha-conotoxins ImI and ImII. Similar alpha 7 nicotinic receptor antagonists act at different sites. J Biol Chem. 2003;278:757-64 pubmed
    ..Like alpha-CTx ImI, the block by alpha-CTx ImII is voltage-independent. Thus, alpha-CTx ImII represents a probe for a novel antagonist binding site, or microsite, on the alpha7 nAChR. ..
  34. Chang L, Lin S, Huang H, Hsiao M. Genetic organization of alpha-bungarotoxins from Bungarus multicinctus (Taiwan banded krait): evidence showing that the production of alpha-bungarotoxin isotoxins is not derived from edited mRNAs. Nucleic Acids Res. 1999;27:3970-5 pubmed
  35. Nirthanan S, Gwee M. Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on. J Pharmacol Sci. 2004;94:1-17 pubmed
    ..This review details the progress made towards achieving this goal. ..
  36. Kulak J, Schneider J. Differences in alpha7 nicotinic acetylcholine receptor binding in motor symptomatic and asymptomatic MPTP-treated monkeys. Brain Res. 2004;999:193-202 pubmed
  37. Khow O, Chanhome L, Omori Satoh T, Sitprija V. Isolation of the major lethal toxin in the venom of Bungarus flaviceps. Toxicon. 2002;40:463-9 pubmed
    ..It is a basic protein consisting of two polypeptide chains having apparent molecular weights of 17 and 8 kDa, respectively. The toxin has PLA activity but is free of ACE activity...
  38. Fabian Fine R, Skehel P, Errington M, Davies H, Sher E, Stewart M, et al. Ultrastructural distribution of the alpha7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci. 2001;21:7993-8003 pubmed
    ..The widespread and substantial expression of alpha7 nAChRs at synapses in the hippocampus is consistent with an important role in mediating and/or modulating synaptic transmission, plasticity, and neurodegeneration. ..
  39. Broide R, Orr Urtreger A, Patrick J. Normal apoptosis levels in mice expressing one alpha7 nicotinic receptor null and one L250T mutant allele. Neuroreport. 2001;12:1643-8 pubmed
    ..Furthermore, L250T mice show normal levels of apoptosis in other nervous system regions expressing alpha7 nAChRs. These results suggest that apoptosis is not the cause of death for L250T neonatal mice. ..
  40. Chung C, Wu B, Yang C, Chang L. Muscarinic toxin-like proteins from Taiwan banded krait (Bungarus multicinctus) venom: purification, characterization and gene organization. Biol Chem. 2002;383:1397-406 pubmed
    ..These results suggest that BM8, BM14, neurotoxins and cardiotoxins may have originated from a common ancestor, and the evolution of snake venom proteins shows a tendency to diversify their functions...
  41. Marutle A, Zhang X, Court J, Piggott M, Johnson M, Perry R, et al. Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. J Chem Neuroanat. 2001;22:115-26 pubmed
  42. St John P, Gordon H. Agonists cause endocytosis of nicotinic acetylcholine receptors on cultured myotubes. J Neurobiol. 2001;49:212-23 pubmed
    ..These results provide direct evidence that agonists, including the tobacco alkaloid nicotine, can cause substantial endocytosis of cell-surface nAChRs. ..
  43. Smit A, Syed N, Schaap D, van Minnen J, Klumperman J, Kits K, et al. A glia-derived acetylcholine-binding protein that modulates synaptic transmission. Nature. 2001;411:261-8 pubmed
    ..We describe a molecular and cellular mechanism by which glial cells release AChBP in the synaptic cleft, and propose a model for how they actively regulate cholinergic transmission between neurons in the central nervous system. ..
  44. Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, et al. alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. J Biol Chem. 2001;276:13541-6 pubmed
    ..These findings indicate that the alpha7 nicotinic receptor transduces signals to PI3K in a cascade, which ultimately contributes to a neuroprotective effect. This might form the basis of a new treatment for AD. ..
  45. Finn A, Feng G, Pendergast A. Postsynaptic requirement for Abl kinases in assembly of the neuromuscular junction. Nat Neurosci. 2003;6:717-23 pubmed
    ..Our findings suggest that Abl kinases provide the developing synapse with the kinase activity required for signal amplification and the intrinsic cytoskeletal regulatory capacity required for assembly and remodeling. ..
  46. Pediconi M, Gallegos C, De Los Santos E, Barrantes F. Metabolic cholesterol depletion hinders cell-surface trafficking of the nicotinic acetylcholine receptor. Neuroscience. 2004;128:239-49 pubmed
  47. Akaaboune M, Culican S, Turney S, Lichtman J. Rapid and reversible effects of activity on acetylcholine receptor density at the neuromuscular junction in vivo. Science. 1999;286:503-7 pubmed
    ..The rapid and reversible alterations in AChR density at the neuromuscular junction in vivo parallel changes thought to occur in the central nervous system at synapses undergoing potentiation and depression. ..
  48. Kasheverov I, Rozhkova A, Zhmak M, Utkin Y, Ivanov V, Tsetlin V. Photoactivatable alpha-conotoxins reveal contacts with all subunits as well as antagonist-induced rearrangements in the Torpedo californica acetylcholine receptor. Eur J Biochem. 2001;268:3664-73 pubmed
  49. Wang Y, Pereira E, Maus A, Ostlie N, Navaneetham D, Lei S, et al. Human bronchial epithelial and endothelial cells express alpha7 nicotinic acetylcholine receptors. Mol Pharmacol. 2001;60:1201-9 pubmed
    ..The presence of alpha7 nAChRs in BEC and AEC suggests that some toxic effects of tobacco smoke could be mediated through these nicotine-sensitive receptors. ..
  50. Palma E, Mileo A, Martinez Torres A, Eusebi F, Miledi R. Some properties of human neuronal alpha 7 nicotinic acetylcholine receptors fused to the green fluorescent protein. Proc Natl Acad Sci U S A. 2002;99:3950-5 pubmed
    ..We also conclude that fused genes do not necessarily recapitulate all of the properties of the original receptors. This fact must be borne close in mind whenever reporter genes are attached to proteins. ..
  51. Tseng W, Lin Shiau S. Activation of NMDA receptor partly involved in beta-bungarotoxin-induced neurotoxicity in cultured primary neurons. Neurochem Int. 2003;42:333-44 pubmed
    ..This snake toxin is considered not only to be a useful tool for exploring the death-signaling pathway of neurotoxicity, but also provides a model for searching neuroprotective agents. ..
  52. Shytle R, Mori T, Townsend K, Vendrame M, Sun N, Zeng J, et al. Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem. 2004;89:337-43 pubmed
    ..Negative regulation of microglia activation may also represent additional mechanism underlying nicotine's reported neuroprotective properties. ..
  53. Das M, Rumsey J, Gregory C, Bhargava N, Kang J, Molnar P, et al. Embryonic motoneuron-skeletal muscle co-culture in a defined system. Neuroscience. 2007;146:481-8 pubmed