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Serotonin transporter phosphorylation modulated by tetanus toxin
Author(s) -
Najib Abderrahim,
Pelliccioni Patricia,
Gil Carles,
Aguilera José
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02294-8
Subject(s) - protein kinase c , phosphorylation , serotonin transporter , internalization , tyrosine phosphorylation , phospholipase c , serotonin , chemistry , biochemistry , biology , microbiology and biotechnology , receptor
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‐α, ‐β and ‐γ) isoforms. The effects on serotonin transport and on c PKC 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 PLCγ1 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.