PMID:1328520

Citation	Presek, P, Jessen, S, Dreyer, F, Jarvie, PE, Findik, D and Dunkley, PR (1992) Tetanus toxin inhibits depolarization-stimulated protein phosphorylation in rat cortical synaptosomes: effect on synapsin I phosphorylation and translocation. J. Neurochem. 59:1336-43
Abstract	Synapsin I, a prominent phosphoprotein in nerve terminals, is proposed to modulate exocytosis by interaction with the cytoplasmic surface of small synaptic vesicles and cytoskeletal elements in a phosphorylation-dependent manner. Tetanus toxin (TeTx), a potent inhibitor of neurotransmitter release, attenuated the depolarization-stimulated increase in synapsin I phosphorylation in rat cortical particles and in synaptosomes. TeTx also markedly decreased the translocation of synapsin I from the small synaptic vesicles and the cytoskeleton into the cytosol, on depolarization of synaptosomes. The effect of TeTx on synapsin I phosphorylation was both time and TeTx concentration dependent and required active toxin. One- and two-dimensional peptide maps of synapsin I with V8 proteinase and trypsin, respectively, showed no differences in the relative phosphorylation of peptides for the control and TeTx-treated synaptosomes, suggesting that both the calmodulin- and the cyclic AMP-dependent kinases that label this protein are equally affected. Phosphorylation of synapsin IIb and the B-50 protein (GAP43), a known substrate of protein kinase C, was also inhibited by TeTx. TeTx affected only a limited number of phosphoproteins and the calcium-dependent decrease in dephosphin phosphorylation remained unaffected. In vitro phosphorylation of proteins in lysed synaptosomes was not influenced by prior TeTx treatment of the intact synaptosomes or by the addition of TeTx to lysates, suggesting that the effect of TeTx on protein phosphorylation was indirect. Our data demonstrate that TeTx inhibits neurotransmitter release, the phosphorylation of a select group of phosphoproteins in nerve terminals, and the translocation of synapsin I. These findings contribute to our understanding of the basic mechanism of TeTx action.
Links	PubMed
Keywords	Animals; Biological Transport/drug effects; Calcium-Calmodulin-Dependent Protein Kinases; Cerebral Cortex/metabolism; Dose-Response Relationship, Drug; Electrophysiology; Osmolar Concentration; Phosphorylation; Protein Kinases/metabolism; Rats; Rats, Sprague-Dawley; Synapsins/metabolism; Synaptosomes/metabolism; Tetanus Toxin/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CLOTE:TETX		GO:0046929: negative regulation of neurotransmitter secretion	ECO:0000314:		P		Figure 1 shows that an increase in Tetanus toxin causes a decrease in noradrenaline release from rat brain cells.	complete CACAO 4572
CLOTE:TETX	involved_in	GO:0046929: negative regulation of neurotransmitter secretion	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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