Susan Amara

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Amara, Susan G.
Detre Professor and Chair, Neurobiology
Ph.D., University of California, San Diego (1983)
Address: 6062 Biomedical Science Tower 3
3501 Fifth Avenue
Pittsburgh, PA 15213-3301
Telephone: 412-383-8910
Fax: 412-383-5267
E-mail: amaras@pitt.edu

Molecular and cellular biology of neurotransmitter transporters.

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.

Prasad, B.M. and Amara, S.G. Dopamine transporter in mesencephalic cultures is refractory to physiological changes in membrane voltage. Journal of Neuroscience 21: 7561-7, 2001.

Seal, R.P., Shigeri, Y., Eliasof, S., Leighton, B.H. and Amara, S.G. Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance. Proceedings of the National Academy of Sciences USA 98: 15324-9, 2001.

Leighton, B.H., Seal, R.P., Shimamoto, K. and Amara, S.G. A hydrophobic domain in glutamate transporters forms an extracellular helix associated with the permeation pathway for substrates. Journal of Biological Chemistry 277:29847-55, 2002.

Ingram, S.L., Prasad, B.M. and Amara, S.G. Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons. Nature Neuroscience 5:971-8, 2002.

Cheng, C., Glover, G., Banker, G. and Amara, S.G. A novel sorting motif in the glutamate transporter EAAT3 directs its targeting in MDCK cells and hippocampal neurons. Journal of Neuroscience 22:10643-52, 2002.