RGD Reference Report - Serotonin transporter phosphorylation modulated by tetanus toxin. - Rat Genome Database

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Serotonin transporter phosphorylation modulated by tetanus toxin.

Authors: Najib, A  Pelliccioni, P  Gil, C  Aguilera, J 
Citation: Najib A, etal., FEBS Lett. 2000 Dec 8;486(2):136-42. doi: 10.1016/s0014-5793(00)02294-8.
RGD ID: 38456013
Pubmed: PMID:11113454   (View Abstract at PubMed)
DOI: DOI:10.1016/s0014-5793(00)02294-8   (Journal Full-text)

Tetanus toxin (TeTx) modifies Na(+)-dependent, high-affinity 5-hydroxytryptamine (5-HT, serotonin) uptake in a synaptosomal-enriched P(2) fraction from rat brain. The effect corresponds to a rapid and non-competitive uptake inhibition, and it is preceded by induction of phospholipase C (PLC) activity and translocation and down-regulation of the classical protein kinase C (PKC-alpha, -beta and -gamma) isoforms. The effects on serotonin transport and on cPKC activation were similar to the effects exhibited by phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Moreover, after treatment with TeTx, an increase in Ser- and Tyr-specific phosphorylation was found. Activation of PKC by both TeTx and TPA results in a loss of transport capacity and serotonin transporter (SERT) phosphorylation, which are abolished by coapplication of the specific PKC inhibitor bisindolylmaleimide-1. Since a specific PLCgamma1 phosphorylation prior to TeTx's inducing SERT phosphorylation was found, the studies suggest that part of the action of TeTx consists of modifying the signal cascade initiated in tyrosine kinase receptors on nerve tissue previous to its cellular internalization, resulting in transporter phosphorylation.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SLC6A4Humanphorbol 13-acetate 12-myristate multiple interactionsISOSlc6a4 (Rattus norvegicus)TPA decreases activity of Slc6a4 protein in synaptosomes and TPA increases phosphorylation of Slc6a4 protein in synaptosomesRGD 
Slc6a4Ratphorbol 13-acetate 12-myristate multiple interactionsEXP TPA decreases activity of Slc6a4 protein in synaptosomes and TPA increases phosphorylation of Slc6a4 protein in synaptosomesRGD 
Slc6a4Mousephorbol 13-acetate 12-myristate multiple interactionsISOSlc6a4 (Rattus norvegicus)TPA decreases activity of Slc6a4 protein in synaptosomes and TPA increases phosphorylation of Slc6a4 protein in synaptosomesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc6a4  (solute carrier family 6 member 4)

Genes (Mus musculus)
Slc6a4  (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4)

Genes (Homo sapiens)
SLC6A4  (solute carrier family 6 member 4)


Additional Information