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Research Description:
Neurotransmitter transporters present on the plasma membrane contribute to the clearance and recycling of neurotransmitters and can have a profound impact on the extent of receptor activation during neuronal signaling. Our major research efforts have focused on the structure, regulation and cellular physiology of two families of sodium-dependent neurotransmitter transporters: the biogenic amine and the excitatory amino acid carriers. The dopamine, norepinephrine and serotonin transporters (DAT, NET and SERT) are well-established targets for addictive drugs including cocaine and amphetamines, and for therapeutic antidepressants. Electrophysiological approaches and imaging techniques have been used to examine the impact of psychostimulant drugs on the signaling properties, physiology and acute regulation of the DAT in cultured midbrain dopamine neurons. In humans, clearance of the major excitatory amino acid neurotransmitter, glutamate, is mediated by five different subtypes of excitatory amino acid transporters (EAATs1-5) found in specific regions of neurons and glial cells. Although these carriers limit CNS concentrations of glutamate, they also possess a ligand-gated chloride channel activity that can regulate neuronal excitability. Our work continues to use molecular genetic, electrophysiological and cell biological approaches to explore the relationships between neurotransmitter transporter structure, substrate transport, inhibitor binding and ion permeation.
Education:
Ph.D., University of California, San Diego (1983)
Important Publications:
- Leighton BH, RP Seal, SD Watts, MO Skyba and SG Amara. Structural rearrangements at the translocation pore of the human glutamate transporter, EAAT1. Journal of Biological Chemistry 281(40):29788-29796, 2006
- Mortensen OV and SG Amara. Gain of function mutants reveal sites important for the interaction of atypical inhibitors benztropine and bupropion with monoamine transporters. Journal of Neurochemistry 98:1531-1540, 2006
- Cheng C, G Glover, G Banker and SG Amara. A novel sorting motif in the glutamate transporter EAAT3 directs its targeting in MDCK cells and hippocampal neurons. Journal of Neuroscience 22:10643-10652, 2002
- Ingram SL, BM Prasad and SG Amara. Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons. Nature Neuroscience 5:971-978, 2002
- Leighton BH, RP Seal, K Shimamoto and SG Amara. A hydrophobic domain in glutamate transporters forms an extracellular helix associated with the permeation pathway for substrates. Journal of Biological Chemistry 277:29847-29855, 2002
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