Document Detail


The glutamate transporter, GLAST, participates in a macromolecular complex that supports glutamate metabolism.
MedLine Citation:
PMID:  22306776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 CO(2) production from radiolabeled glutamate in cultured astrocytes and compared it to overall glutamate uptake. Within 15 min, 9% of transported glutamate was converted to CO(2). This CO(2) 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.
Authors:
Deborah E Bauer; Joshua G Jackson; Elizabeth N Genda; Misty M Montoya; Marc Yudkoff; Michael B Robinson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-28
Journal Detail:
Title:  Neurochemistry international     Volume:  61     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-07     Completed Date:  2013-02-11     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  566-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebellum / metabolism
Excitatory Amino Acid Transporter 1 / physiology*
Glutamic Acid / metabolism*
Humans
Male
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
K12 GM081259/GM/NIGMS NIH HHS; K12 GM081259-03S1/GM/NIGMS NIH HHS; K12GM081259/GM/NIGMS NIH HHS; P30 HD026979-20/HD/NICHD NIH HHS; P30HD26979/HD/NICHD NIH HHS; R01 NS077773/NS/NINDS NIH HHS; R25 GM071745/GM/NIGMS NIH HHS; R25 GM071745-08/GM/NIGMS NIH HHS; R25GM071745/GM/NIGMS NIH HHS; T32 NS007413/NS/NINDS NIH HHS; T32 NS007413-12S1/NS/NINDS NIH HHS; T32NS007413/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Transporter 1; 0/SLC1A3 protein, human; 3KX376GY7L/Glutamic Acid
Comments/Corrections

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