Activation of signal transduction pathways involving trkA, PLCgamma-1, PKC isoforms and ERK-1/2 by tetanus toxin.

Previous reports have demonstrated that tetanus toxin (TeTx) induces activation and down-regulation of protein kinase C (PKC). In the present work the differential activation of PKC isoforms and of signal transduction pathways, including nerve growth factor receptor trkA, phospholipase Cgamma-1 (PLCgamma-1), and extracellular regulated kinases 1 and 2 (ERK-1/2) by TeTx in a synaptosome-enriched P(2) fraction from rat brain is reported. TeTx induces clear translocation from the soluble (cytosolic) compartment to the particulate (membranous) compartment of PKC-beta, -gamma and -delta isoforms, whereas PKC-epsilon showed a slight decrease of its soluble fraction immunoreactivity. On the contrary, the PKC-zeta isoform shows no consistent response, whereas down-regulation of total PKC-alpha immunoreactivity is shown. Immunoprecipitation assays against phosphotyrosine show an increase of trkA and PLCgamma-1 phosphorylation. Moreover, trkA activation is corroborated using phospho-specific antibodies against phosphorylated trkA. On the other hand, TeTx-induced stimulation of mitogen-activated protein (MAP) kinase activity is observed, this event also being detected by Western analysis using phospho-specific antibodies against ERK-1/2.