CNUP Training Faculty, Detre Professor and Chair, Neurobiology University of Pittsburgh Phone: 412-383-8910 Fax: 412-383-8910 Email: amaras@pitt.edu

Ph. D., University of California, San Diego (1983)

Research Interests

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.

Publications

• Cheng C, Glover G, Banker G, Amara SG: A novel sorting motif in the glutamate transporter EAAT3 directs its targeting in MDCK cells and hippocampal neurons. J Neurosci 22: 10643-52, 2002.
• Ingram SL, Prasad BM, Amara SG: Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons. Nat Neurosci 5: 971-8, 2002.
• Leighton BH, Seal RP, Shimamoto K, Amara SG: A hydrophobic domain in glutamate transporters forms an extracellular helix associated with the permeation pathway for substrates. J Biol Chem 277: 29847- 55, 2002.
• Prasad BM. Amara SG: Dopamine transporter in mesencephalic cultures is refractory to physiological changes in membrane voltage. J Neuro 21: 7561-7, 2001.
• Seal RP, Shigeri Y, Eliasof S, Leighton BH, Amara SG: Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance. Proc Natl Acad Sci USA 98: 15324-9, 2001.