Journal article
Co-compartmentalization of the Astroglial Glutamate Transporter, GLT-1, with Glycolytic Enzymes and Mitochondria
The Journal of neuroscience, v 31(50), pp 18275-18288
14 Dec 2011
PMID: 22171032
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Efficient excitatory transmission depends on a family of transporters that use the Na+-electrochemical gradient to maintain low synaptic concentrations of glutamate. These transporters consume substantial energy in the spatially restricted space of fine astrocytic processes. GLT-1 (EAAT2) mediates the bulk of this activity in forebrain. To date, relatively few proteins have been identified that associate with GLT-1. In the present study, GLT-1 immunoaffinity isolates were prepared from rat cortex using three strategies and analyzed by liquid chromatography-coupled tandem mass spectrometry. In addition to known interacting proteins, the analysis identified glycolytic enzymes and outer mitochondrial proteins. Using double-label immunofluorescence, GLT-1 was shown to colocalize with the mitochondrial matrix protein, ubiquinol-cytochrome c reductase core protein 2 or the inner mitochondrial membrane protein, ADP/ATP translocase, in rat cortex. In biolistically transduced hippocampal slices, fluorescently tagged GLT-1 puncta overlapped with fluorescently tagged mitochondria along fine astrocytic processes. In a Monte Carlo-type computer simulation, this overlap was significantly more frequent than would occur by chance. Furthermore, fluorescently tagged hexokinase-1 overlapped with mitochondria or GLT-1, strongly suggesting that GLT-1, mitochondria, and the first step in glycolysis are cocompartmentalized in astrocytic processes. Acute inhibition of glycolysis or oxidative phosphorylation had no effect on glutamate uptake in hippocampal slices, but simultaneous inhibition of both processes significantly reduced transport. Together with previous results, these studies show that GLT-1 cocompartmentalizes with Na+/K+ ATPase, glycolytic enzymes, and mitochondria, providing a mechanism to spatially match energy and buffering capacity to the demands imposed by transport.
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Details
- Title
- Co-compartmentalization of the Astroglial Glutamate Transporter, GLT-1, with Glycolytic Enzymes and Mitochondria
- Creators
- Elizabeth N. Genda - Children's Hospital of PhiladelphiaJoshua G. Jackson - Children's Hospital of PhiladelphiaAmanda L. Sheldon - Children's Hospital of PhiladelphiaSusannah F. Locke - Children's Hospital of PhiladelphiaTodd M. Greco - Children's Hospital of PhiladelphiaJohn C. O'Donnell - Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USALynn A. Spruce - Children's Hospital of PhiladelphiaRui Xiao - University of PennsylvaniaWensheng Guo - University of PennsylvaniaMary Putt - University of PennsylvaniaSteven Seeholzer - Children's Hospital of PhiladelphiaHarry Ischiropoulos - Children's Hospital of PhiladelphiaMichael B. Robinson - Children's Hospital of Philadelphia
- Publication Details
- The Journal of neuroscience, v 31(50), pp 18275-18288
- Publisher
- Soc Neuroscience
- Number of pages
- 14
- Grant note
- Analytical Neurochemistry Core R01NS077773 / 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) Biostatistics and Bioinformatics Core Cellular Neuroscience Core P30 HD26979 / Institutional Intellectual and Developmental Disabilities Research Center Genetics Core 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)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000298055600008
- Scopus ID
- 2-s2.0-83455179198
- Other Identifier
- 991021900018604721
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- Web of Science research areas
- Neurosciences