![]() | ||||||||||||||
|
Meet the Lab | PI | Representative Publications | Training Opportunities | |||||||||||||
![]() |
Amara, Susan G. 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.
| ||||||||||||||
![]() | ||||||||||||||
![]() |
Copyright 2001 - University
of Pittsburgh Department of Neurobiology | |||||||||||||