Distribution of Glutamate Transporter GLAST in Membranes of Cultured Astrocytes in the Presence of Glutamate Transport Substrates and ATP |
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Authors: | Jae-Won Shin Khoa T D Nguyen David V Pow Toby Knight Vlado Buljan Maxwell R Bennett Vladimir J Balcar |
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Institution: | (1) Anatomy and Histology, School of Medical Sciences and Bosch Institute for Biomedical Research, The University of Sydney, Sydney, NSW, 2006, Australia;(2) Centre for Clinical Research, Royal Brisbane and Womens Hospital, The University of Queensland, Brisbane, QLD, 4029, Australia;(3) Brain and Mind Research Institute, The University of Sydney, Sydney, NSW, 2006, Australia |
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Abstract: | Neurotransmitter l-glutamate released at central synapses is taken up and “recycled” by astrocytes using glutamate transporter molecules such
as GLAST and GLT. Glutamate transport is essential for prevention of glutamate neurotoxicity, it is a key regulator of neurotransmitter
metabolism and may contribute to mechanisms through which neurons and glia communicate with each other. Using immunocytochemistry
and image analysis we have found that extracellular d-aspartate (a typical substrate for glutamate transport) can cause redistribution of GLAST from cytoplasm to the cell membrane.
The process appears to involve phosphorylation/dephosphorylation and requires intact cytoskeleton. Glutamate transport ligands
l
-trans-pyrrolidine-2,4-dicarboxylate and dl-threo-3-benzyloxyaspartate but not anti,endo-3,4-methanopyrrolidine dicarboxylate have produced similar redistribution of GLAST. Several representative ligands for glutamate
receptors whether of ionotropic or metabotropic type, were found to have no effect. In addition, extracellular ATP induced
formation of GLAST clusters in the cell membranes by a process apparently mediated by P2 receptors. The present data suggest
that GLAST can rapidly and specifically respond to changes in the cellular environment thus potentially helping to fine-tune
the functions of astrocytes.
The authors J.-W. Shin and K. T. D. Nguyen have contributed equally. |
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Keywords: | Astrocytes Glutamate synapses Glutamate transport GLAST GLT Brain metabolism Na+ K+-dependent ATPase Neurotransmitter metabolism Regulation of transporters Phosphorylation and dephosphorylation of membrane proteins |
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