Related Experiment Videos
Serotonin transporter phosphorylation modulated by tetanus toxin.
A Najib1, P Pelliccioni, C Gil
1Departament de Bioquímica i de Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Cerdanyola del Vallés, Barcelona, Spain.
FEBS Letters
|December 13, 2000
Summary
Tetanus toxin (TeTx) inhibits serotonin uptake by affecting protein kinase C (PKC) and phospholipase C (PLC) signaling pathways. This neurotoxin
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Signaling
Background:
- Tetanus toxin (TeTx) is known to affect neuronal function.
- Serotonin (5-HT) uptake is crucial for neurotransmission.
- Protein kinase C (PKC) and phospholipase C (PLC) are key signaling enzymes.
Purpose of the Study:
- To investigate the molecular mechanisms by which TeTx affects serotonin uptake in rat brain synaptosomes.
- To elucidate the role of PKC and PLC in TeTx-induced alterations of serotonin transport.
Main Methods:
- Preparation of synaptosomal-enriched P(2) fraction from rat brain.
- Measurement of Na(+)-dependent, high-affinity 5-HT uptake.
- Assay of phospholipase C (PLC) activity.
- Western blot analysis for PKC isoform translocation and phosphorylation.
- Inhibition studies using a specific PKC inhibitor.
Main Results:
- TeTx rapidly and non-competitively inhibited 5-HT uptake.
- TeTx induced PLC activity and altered PKC isoform localization and activity.
- Phorbol ester (TPA) mimicked TeTx's effects on 5-HT transport and PKC activation.
- TeTx and TPA treatment led to increased Ser- and Tyr-specific phosphorylation of the serotonin transporter (SERT).
- PKC inhibition abolished TeTx-induced SERT phosphorylation and transport inhibition.
Conclusions:
- TeTx modulates serotonin uptake via activation of PLC and PKC signaling pathways.
- TeTx-induced SERT phosphorylation is mediated by PKC activation.
- The findings suggest TeTx modifies signal cascades involving tyrosine kinase receptors, leading to SERT phosphorylation.