Glutamate transport is an essential component of central glutamatergic neurotransmission; studies document an essential role for glutamate transport in the inactivation of synaptically released glutamate and the prevention of excitotoxicity. The understanding of glutamatergic neurotransmission has expanded recently with the identification of new proteins responsible for the regulation and synaptic targeting of these receptors to the synaptic cleft. Studies also suggest that glutamate transporters may be regulated and targeted to the synaptic cleft. We hypothesize that neuronal proteins exist that are responsible for the synaptic targeting and regulation of neuronal glutamate transporter subtypes; we propose to label these proteins GTRAP: glutamate transporter associated protein. In preliminary studies we have identified at least three novel and specific interacting proteins that appear to both positively and negatively modulate neuronal glutamate transporter subtypes. We will identify proteins that interact with the major intracellular domains of the two neuronal glutamate transporter subtypes: EAAT4 and EAACI (EAAT3).
The aims of the studies include: 1) Identification and characterization of neuronal glutamate transporter interacting proteins. Using yeast-two hybrid screens, we will identify proteins that interact with both neuronal glutamate transporter subtypes; 2) Determine the specificity and characterization of GTRAP-transporter interaction. 3) Evaluate the cellular and ultrastructural distribution of GTRAPs and 4) to determine the physiological regulation of neuronal glutamate transporters by these novel GTRAPs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040151-03
Application #
6540276
Study Section
Special Emphasis Panel (ZRG1-MDCN-2 (01))
Program Officer
Tagle, Danilo A
Project Start
2000-05-15
Project End
2005-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
3
Fiscal Year
2002
Total Cost
$293,599
Indirect Cost
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Ganel, Raquelli; Ho, Tony; Maragakis, Nicholas J et al. (2006) Selective up-regulation of the glial Na+-dependent glutamate transporter GLT1 by a neuroimmunophilin ligand results in neuroprotection. Neurobiol Dis 21:556-67
Sepkuty, Jehuda P; Cohen, Akiva S; Eccles, Christine et al. (2002) A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy. J Neurosci 22:6372-9