XB-ART-23191
Proc Natl Acad Sci U S A
November 15, 1992;
89
(22):
10955-9.
Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain.
Storck T
,
Schulte S
,
Hofmann K
,
Stoffel W
.
Abstract
Transport systems specific for L-glutamate and L-aspartate play an important role in the termination of neurotransmitter signals at excitatory synapses. We describe here the structure and function of a 66-kDa glycoprotein that was purified from rat
brain and identified as an L-glutamate/L-aspartate transporter (
GLAST). A
GLAST-specific cDNA clone was isolated from a rat
brain cDNA library. The cDNA insert encodes a polypeptide with 543 amino acid residues (59,697 Da). The amino acid sequence of
GLAST suggests a distinctive structure and membrane topology, with some conserved motifs also present in prokaryotic glutamate transporters. The transporter function has been verified by amino acid uptake studies in the Xenopus laevis
oocyte system.
GLAST is specific for L-glutamate and L-aspartate, shows strict dependence on Na+ ions, and is inhibited by DL-threo-3-hydroxy-aspartate. In situ hybridization reveals a strikingly high density of
GLAST mRNA in the Purkinje cell layer of
cerebellum, presumably in the Bergmann
glia cells, and a less dense distribution throughout the cerebrum. These data suggest that
GLAST may be involved in the regulation of neurotransmitter concentration in
central nervous system.
PubMed ID:
1279699
PMC ID:
PMC50461
Article link:
Proc Natl Acad Sci U S A
Species referenced:
Xenopus laevis
Genes referenced:
slc1a3
References [+] :
Balcar,
The structural specificity of the high affinity uptake of L-glutamate and L-aspartate by rat brain slices.
1973,
Pubmed
Balcar,
The structural specificity of the high affinity uptake of L-glutamate and L-aspartate by rat brain slices.
1973,
Pubmed
Blakely,
Cloning and expression of a functional serotonin transporter from rat brain.
1991,
Pubmed
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
Danbolt,
Purification and reconstitution of the sodium- and potassium-coupled glutamate transport glycoprotein from rat brain.
1990,
Pubmed
Deguchi,
Nucleotide sequence of gltS, the Na+/glutamate symport carrier gene of Escherichia coli B.
1991,
Pubmed
Drejer,
Characterization of uptake and release processes for D- and L-aspartate in primary cultures of astrocytes and cerebellar granule cells.
1983,
Pubmed
Eisenberg,
Analysis of membrane and surface protein sequences with the hydrophobic moment plot.
1984,
Pubmed
Flott,
Characterization of glutamate uptake systems in astrocyte primary cultures from rat brain.
1991,
Pubmed
Fonnum,
Glutamate: a neurotransmitter in mammalian brain.
1984,
Pubmed
Gordon,
Partial purification of the sodium- and potassium-coupled L-glutamate transport glycoprotein from rat brain.
1988,
Pubmed
Guastella,
Cloning and expression of a rat brain GABA transporter.
1990,
Pubmed
,
Xenbase
Hoffman,
Cloning of a serotonin transporter affected by antidepressants.
1991,
Pubmed
Hollmann,
Glutamate transport and not glutamate receptor binding is stimulated by gangliosides in a Ca2+-dependent manner in rat brain synaptic plasma membranes.
1989,
Pubmed
Hollmann,
Calcium ions induce glutamate transport into rat brain membrane vesicles in the absence of sodium and chloride. Evidence for a novel uptake site?
1988,
Pubmed
Jiang,
Conservation between coding and regulatory elements of Rhizobium meliloti and Rhizobium leguminosarum dct genes.
1989,
Pubmed
Kalman,
Characterization of the Escherichia coli K12 gltS glutamate permease gene.
1991,
Pubmed
Kilty,
Cloning and expression of a cocaine-sensitive rat dopamine transporter.
1991,
Pubmed
Kimelberg,
Excitatory amino acid-stimulated uptake of 22Na+ in primary astrocyte cultures.
1989,
Pubmed
Kurth,
A facile method for the isolation and preparation of proteins and peptides for sequence analysis in the picomolar range.
1990,
Pubmed
Kyte,
A simple method for displaying the hydropathic character of a protein.
1982,
Pubmed
Logan,
Unique high affinity uptake systems for glycine, glutamic and aspartic acids in central nervous tissue of the rat.
1972,
Pubmed
McBean,
Neurotoxicity of L-glutamate and DL-threo-3-hydroxyaspartate in the rat striatum.
1985,
Pubmed
Monaghan,
The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system.
1989,
Pubmed
Okamoto,
Synaptic receptors and intracellular signal transduction in the cerebellum.
1991,
Pubmed
Pacholczyk,
Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter.
1991,
Pubmed
Palmer,
Excitatory amino acid-releasing and cholinergic neurones in Alzheimer's disease.
1986,
Pubmed
Pin,
The Ca2+/C1- dependent L-[3H]glutamate binding: a new receptor or a particular transport process?
1984,
Pubmed
Pines,
Counterflow of L-glutamate in plasma membrane vesicles and reconstituted preparations from rat brain.
1991,
Pubmed
Sanger,
DNA sequencing with chain-terminating inhibitors.
1978,
Pubmed
Schägger,
Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa.
1988,
Pubmed
Shimada,
Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA.
1991,
Pubmed
,
Xenbase
Tolner,
Revised nucleotide sequence of the gltP gene, which encodes the proton-glutamate-aspartate transport protein of Escherichia coli K-12.
1992,
Pubmed
Usdin,
Cloning of the cocaine-sensitive bovine dopamine transporter.
1992,
Pubmed
Waniewski,
Characterization of L-glutamic acid transport by glioma cells in culture: evidence for sodium-independent, chloride-dependent high affinity influx.
1984,
Pubmed
Zaczek,
Quisqualate-sensitive, chloride-dependent transport of glutamate into rat brain synaptosomes.
1988,
Pubmed