Blakely Lab

The Blakely Lab

Regulated Trafficking of Neurotransmitter Transporters

Neurotransmitter transporters have the capacity to alter chemical signaling in the nervous system. Recent studies have indicated that many of these proteins are not constitutively expressed at the plasma membrane but are recruited to or withdrawn from the cell surface in response to receptor activation, elevated second messengers and activated protein kinases/phosphatases.

We have demonstrated that SERT proteins are phosphorylated following PKC activation or PP1/2A inhibition. Similar findings are evident for DA and NE transporters (DAT and NET respectively). Many issues remain unresolved here. Exactly which kinases and phosphatases target these transporters is unclear, though increasing evidence points to an important role for isoforms of PKC and PP2A.

Recently, our group has shown that the PP2A catalytic subunit physically associates with SERT, NET and DAT proteins in a regulated manner. This association may provide a mechanism to limit transporter phosphorylation or the phosphorylation of an associated protein. One protein that has increasingly drawn our attention is syntaxin 1, a plasma membrane protein involved in neurotransmitter release.

Our findings with NET proteins support data obtained by others with GAT1 and glycine transporters that syntaxin, like PP2A, forms reversible associations with biogenic amine transporters that may be linked to altered surface expression or intrinsic changes in transporter activity.