0000000000117849

AUTHOR

J. Oliver Dolly

showing 3 related works from this author

Tetanus Toxin Inhibits Neuroexocytosis Even When Its Zn2+-dependent Protease Activity Is Removed

1995

Tetanus toxin (TeTX) is a dichain protein that blocks neuroexocytosis, an action attributed previously to Zn(2+)-dependent proteolysis of synaptobrevin (Sbr) by its light chain (LC). Herein, its cleavage of Sbr in rat cerebrocortical synaptosomes was shown to be minimized by captopril, an inhibitor of certain metalloendoproteases, whereas this agent only marginally antagonized the inhibition of noradrenaline release, implicating a second action of the toxin. This hypothesis was proven by preparing three mutants (H233A, E234A, H237A) of the LC lacking the ability to cleave Sbr and reconstituting them with native heavy chain. The resultant dichains were found to block synaptosomal transmitter…

CaptoprilSynaptobrevinProteolysismedicine.medical_treatmentGuinea PigsInhibitory postsynaptic potentialmedicine.disease_causeBiochemistryExocytosisNorepinephrinechemistry.chemical_compoundTetanus ToxinCadaverineAplysiaEndopeptidasesmedicineAnimalsEnzyme InhibitorsNeurotransmitterMolecular BiologyCerebral CortexTransglutaminasesProteasemedicine.diagnostic_testbiologyToxinHydrolysisWild typeCell Biologybiology.organism_classificationRecombinant ProteinsRatsZincBiochemistrychemistryAplysiaBiophysicsSynaptosomesJournal of Biological Chemistry
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Differences in the temperature dependencies of uptake of botulinum and tetanus toxins in Aplysia neurons

1992

The respective neuroselective actions of botulinum type A (BoNT) and tetanus (TeTx) neurotoxins on cholinergic and non-cholinergic synapses of Aplysia are mainly due to differences in their extracellular neuronal targetting. Further information was gained on this neuroselectivity by examining the temperature dependencies of binding, internalization and intracellular action of both toxins. After reduction of temperature from 22 degrees C to 10 degrees C, the binding of neither BoNT nor TeTx was significantly altered whereas the neuronal uptake of BoNT, but not of TeTx, was prevented. Although TeTx internalization could be detected at the low temperature, its intracellular activity was greatl…

NeuronsBotulinum ToxinsGeneral Neurosciencemedia_common.quotation_subjectTemperatureBiologybiology.organism_classificationAcetylcholineSynapseTetanus ToxinAplysiaAplysiamedicineExtracellularBiophysicsAnimalsNeurotoxinCholinergicInternalizationNeuroscienceAcetylcholineIntracellularmedia_commonmedicine.drugNeuroscience Letters
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Botulinum A and the light chain of tetanus toxins inhibit distinct stages of Mg.ATP-dependent catecholamine exocytosis from permeabilised chromaffin …

1994

Susceptibilities of Mg.ATP-independent and Mg.ATP-requiring components of catecholamine secretion from digitonin-permeabilised chromaffin cells to inhibition by Clostridial botulinum type A and tetanus toxins were investigated. These toxins are Zn(2+)-dependent proteases which specifically cleave the 25-kDa synaptosomal-associated protein (SNAP-25) and vesicle-associated membrane protein (VAMP) II, respectively. When applied to permeabilised chromaffin cells they rapidly inhibited secretion in the presence of Mg.ATP but the catecholamine released in the absence of Mg.ATP, thought to represent fusion of primed granules, was not perturbed. The toxins can exert their effects per se in the abse…

ProteasesBotulinum ToxinsCell Membrane PermeabilityBiologymedicine.disease_causeBiochemistryExocytosisExocytosischemistry.chemical_compoundAdenosine TriphosphateCatecholaminesTetanus ToxinmedicineAnimalsSecretionChromaffin GranulesCells CulturedToxinKineticsmedicine.anatomical_structurechemistryMembrane proteinBiochemistryAdrenal MedullaCatecholamineCattleAdrenal medullaAdenosine triphosphatemedicine.drugEuropean journal of biochemistry
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