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Journal article
The glutamate transporter, GLAST, participates in a macromolecular complex that supports glutamate metabolism
Neurochemistry international, v 61(4), pp 566-574
01 Sep 2012
PMID: 22306776
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
GLAST is the predominant glutamate transporter in the cerebellum and contributes substantially to glutamate transport in forebrain. This astroglial glutamate transporter quickly binds and clears synaptically released glutamate and is principally responsible for ensuring that synaptic glutamate concentrations remain low. This process is associated with a significant energetic cost. Compartmentalization of GLAST with mitochondria and proteins involved in energy metabolism could provide energetic support for glutamate transport. Therefore, we performed immunoprecipitation and co-localization experiments to determine if GLAST might co-compartmentalize with proteins involved in energy metabolism. GLAST was immunoprecipitated from rat cerebellum and subunits of the Na+/K+ ATPase, glycolytic enzymes, and mitochondrial proteins were detected. GLAST co-localized with mitochondria in cerebellar tissue. GLAST also co-localized with mitochondria in fine processes of astrocytes in organotypic hippocampal slice cultures. From these data, we hypothesized that mitochondria participate in a macromolecular complex with GLAST to support oxidative metabolism of transported glutamate. To determine the functional metabolic role of this complex, we measured CO2 production from radiolabeled glutamate in cultured astrocytes and compared it to overall glutamate uptake. Within 15 min, 9% of transported glutamate was converted to CO2. This CO2 production was blocked by inhibitors of glutamate transport and glutamate dehydrogenase, but not by an inhibitor of glutamine synthetase. Our data support a model in which GLAST exists in a macromolecular complex that allows transported glutamate to be metabolized in mitochondria to support energy production. (C) 2012 Elsevier Ltd. All rights reserved.
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Details
- Title
- The glutamate transporter, GLAST, participates in a macromolecular complex that supports glutamate metabolism
- Creators
- Deborah E. Bauer - University of PennsylvaniaJoshua G. Jackson - Children's Hospital of PhiladelphiaElizabeth N. Genda - Children's Hospital of PhiladelphiaMisty M. Montoya - Children's Hospital of PhiladelphiaMarc Yudkoff - Children's Hospital of PhiladelphiaMichael B. Robinson - University of Pennsylvania
- Publication Details
- Neurochemistry international, v 61(4), pp 566-574
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- K12GM081259 / Institutional Research and Academic Career Development Award T32NS007413 / Training Grant in Neurodevelopmental Disabilities R25GM071745 / University of Pennsylvania Postbaccalaureate Research Education Program P30HD026979 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) T32NS007413 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) K12GM081259 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P30HD26979 / Analytical Neurochemistry Core of the Institutional Intellectual and Developmental Disabilities Research Center
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000309623600016
- Scopus ID
- 2-s2.0-84865735219
- Other Identifier
- 991021900192304721
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InCites Highlights
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences