Eric Buck

The elucidation of the mechanisms underlying regulation of the pre-synaptic serotonin transporter (SERT) is crucial to the understanding of serotonin neurotransmission and is a major focus of investigation.  We have previously documented that SERT is phosphorylated in response to protein kinase C (PKC) activation and that phosphatase inhibition decreases SERT activity and its surface distribution.  Increasing SERT activity also attenuates PKC mediated SERT phosphorylation and sequestration.  We are currently investigating the cyclic GMP (cGMP)-linked second messenger systems involved in SERT regulation. Our studies provide evidence that in the CNS, PKC activation stimulates endogenous SERT activity in a trafficking-independent mechanism that is accompanied by SERT phosphorylation with increased SERT-PP2Ac and syntaxin 1A interaction.