Genomes and Genes
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.
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- 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. ..
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- Cheng Y, Chen K, Lin S, Chang L. Divergence of genes encoding B chains of beta-bungarotoxins. Toxicon. 2006;47:322-9 pubmedThe structural organization of the genes encoding B2, B4, B5 and B6 chains of beta-bungarotoxins are reported in this study...
- 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. ..
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- 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. ..
- 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. ..
- 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...
- 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. ..
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- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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
- 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
- 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. ..
- 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. ..
- 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
- 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. ..
- 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
- 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...
- 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. ..
- 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. ..
- 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...
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
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