Publications

• A current view of serotonin transporters.

  De Felice L.J.

  Serotonin transporters (SERTs) are largely recognized for one aspect of their function-to transport serotonin back into the presynaptic terminal after its release. Another aspect of their function, however, may be to generate currents large enough to have physiological consequences. The standard m ... >> More

  Serotonin transporters (SERTs) are largely recognized for one aspect of their function-to transport serotonin back into the presynaptic terminal after its release. Another aspect of their function, however, may be to generate currents large enough to have physiological consequences. The standard model for electrogenic transport is the alternating access model, in which serotonin is transported with a fixed ratio of co-transported ions resulting in net charge per cycle. The alternating access model, however, cannot account for all the observed currents through SERT or other monoamine transporters.  Furthermore, SERT agonists like ecstasy or antagonists like fluoxetine generate or suppress currents that the standard model cannot support.  Here we survey evidence for a channel mode of transport in which transmitters and ions move through a pore. Available structures for dopamine and serotonin transporters, however, provide no evidence for a pore conformation, raising questions of whether the proposed channel mode actually exists or whether the structural data are perhaps missing a transient open state. << Less

  F1000Res 5:F1000 Faculty 2016:Rev-1884(2016) [PubMed] [EuropePMC]

• Protein kinase C activation regulates human serotonin transporters in HEK-293 cells via altered cell surface expression.

  Qian Y., Galli A., Ramamoorthy S., Risso S., DeFelice L.J., Blakely R.D.

  Antidepressant- and cocaine-sensitive serotonin (5-hydroxytryptamine, 5-HT) transporters (SERTs) dictate clearance of extracellular 5-HT after release. To explore protein kinase C-mediated SERT regulation, we generated a stable human SERT (hSERT)-expressing cell line (293-hSERT) and evaluated modu ... >> More

  Antidepressant- and cocaine-sensitive serotonin (5-hydroxytryptamine, 5-HT) transporters (SERTs) dictate clearance of extracellular 5-HT after release. To explore protein kinase C-mediated SERT regulation, we generated a stable human SERT (hSERT)-expressing cell line (293-hSERT) and evaluated modulation of 5-HT activity via studies of 5-HT flux, hSERT-mediated currents under voltage clamp, and surface distribution of SERT protein. 293-hSERT cells exhibit saturable, high-affinity, and antidepressant-sensitive 5-HT uptake as well as hSERT-dependent whole-cell currents. In these cells, the protein kinase C activator beta-PMA caused a time-dependent reduction in 5-HT uptake capacity (Vmax) after acute application and a reduction in SERT-mediated currents. Effects of beta-PMA were mimicked by the phorbol ester beta-PDBu, were not observed with the inactive alpha-isomers, and could be blocked by treatment of cells with the protein kinase C inhibitor staurosporine. Biotinylation/immunoblot analyses showed that activity reductions are paralleled by a staurosporine-sensitive loss of surface SERT protein. These data indicate that altered surface abundance, rather than reduced catalytic transport efficiency, mediates acute PKC-dependent modulation of 5-HT uptake. << Less

  J Neurosci 17:45-57(1997) [PubMed] [EuropePMC]

• The role of chloride ion in platelet serotonin transport.

  Nelson P.J., Rudnick G.

  Chloride ion is required for platelet serotonin transport. This anion requirement is relatively specific for Cl-. Only Br-fully substitutes, while SCN-, NO2-, and NO3-are much less effective. Serotonin influx requires external Cl-, and efflux requires internal Cl-. Although internal Cl-is not requ ... >> More

  Chloride ion is required for platelet serotonin transport. This anion requirement is relatively specific for Cl-. Only Br-fully substitutes, while SCN-, NO2-, and NO3-are much less effective. Serotonin influx requires external Cl-, and efflux requires internal Cl-. Although internal Cl-is not required for transport and has little effect on the initial rate of influx, it decreases the steady state level of serotonin accumulation. Chloride ion does not merely fulfill a need for a permanent ion since it is required for exchange of internal with external serotonin. Moreover, serotonin accumulation still requires external Cl-when a K+ diffusion potential (interior negative) is imposed across the vesicle membrane with valinomycin. Furthermore, Cl-lowers the Km and raises the Vmax for transport, suggesting direct effects on the transporter. These results strongly suggest serotonin-Cl-co-transport across the platelet plasma membrane. << Less

  J Biol Chem 257:6151-6155(1982) [PubMed] [EuropePMC]