Susan Amara

Amara, Susan G.
Detre Professor and Chair, Neurobiology
Ph.D., University of California, San Diego (1983)
Address: 6062 BST3
3501 Fifth Avenue
Pittsburgh, PA 15213-3301
Telephone: 412-383-8910
Fax: 412-383-5267
E-mail: amaras@pitt.edu
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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.

Sample Publications:

Large collective motions regulate the functional properties of glutamate transporter trimers.
Jiang J, Shrivastava IH, Watts SD, Bahar I, Amara SG.
Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15141-6.

Dopamine transport by the serotonin transporter: a mechanistically distinct mode of substrate translocation.
Larsen MB, Sonders MS, Mortensen OV, Larson GA, Zahniser NR, Amara SG.
J Neurosci. 2011 Apr 27;31(17):6605-15.

New views of glutamate transporter structure and function: Advances and challenges.
Jiang J, Amara SG.
Neuropharmacology. 2011 Jan;60(1):172-81.

Membrane cholesterol modulates the outward-facing conformation of the dopamine transporter and alters cocaine binding.
Hong WC, Amara SG.
J Biol Chem. 2010 Oct 15;285(42):32616-26.

Close encounters of the oily kind: regulation of transporters by lipids.
Divito CB, Amara SG.
Mol Interv. 2009 Oct;9(5):252-62. Review.

Molecular simulations elucidate the substrate translocation pathway in a glutamate transporter.
Gu Y, Shrivastava IH, Amara SG, Bahar I.
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2589-94.

Genetic Complementation Screen Identifies a Mitogen-activated Protein Kinase Phosphatase, MKP3, as a Regulator of Dopamine Transporter Trafficking.
Mortensen OV, Larsen MB, Prasad BM, Amara SG.
Mol Biol Cell. 2008 Jul;19(7):2818-29.

Chloride finds its place in the transport cycle.
Amara SG.
Nat Struct Mol Biol. 2007 Sep;14(9):792-4.

Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom.
Fontana AC, de Oliveira Beleboni R, Wojewodzic MW, Ferreira Dos Santos W, Coutinho-Netto J, Grutle NJ, Watts SD, Danbolt NC, Amara SG.
Mol Pharmacol. 2007 Nov;72(5):1228-37.

Glutamate and monoamine transporters: new visions of form and function.
Torres GE, Amara SG.
Curr Opin Neurobiol. 2007 Jun;17(3):304-12. Review.

Structural rearrangements at the translocation pore of the human glutamate transporter, EAAT1.
Leighton BH, Seal RP, Watts SD, Skyba MO, Amara SG.
J Biol Chem. 2006 Oct 6;281(40):29788-96.

Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons.
Ingram SL, Prasad BM, Amara SG.
Nat Neurosci. 2002 Oct;5(10):971-8.

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