Excitatory amino acid transporter 1

Excitatory amino acid transporter 1 (EAAT1) is a protein that, in humans, is encoded by the SLC1A3 gene.^[5] EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1).

SLC1A3
Identifiers
Aliases	SLC1A3, EA6, EAAT1, GLAST, GLAST1, solute carrier family 1 member 3
External IDs	OMIM: 600111; MGI: 99917; HomoloGene: 20882; GeneCards: SLC1A3; OMA:SLC1A3 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5p13.2 Start 36,596,588 bp[1] End 36,688,334 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 A1|15 3.82 cM Start 8,663,608 bp[2] End 8,740,248 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone dorsal motor nucleus of vagus nerve internal globus pallidus external globus pallidus Region I of hippocampus proper inferior olivary nucleus nucleus accumbens middle temporal gyrus optic nerve Amygdala Top expressed in lobe of cerebellum cerebellar vermis lateral septal nucleus paraventricular nucleus of hypothalamus arcuate nucleus globus pallidus dorsomedial hypothalamic nucleus lateral hypothalamus ventromedial nucleus anterior amygdaloid area More reference expression data BioGPS More reference expression data
Gene ontology Molecular function amino acid binding symporter activity glutamate binding L-glutamate transmembrane transporter activity amino acid transmembrane transporter activity high-affinity glutamate transmembrane transporter activity acidic amino acid transmembrane transporter activity glutamate:sodium symporter activity metal ion binding Cellular component integral component of membrane cell projection membrane plasma membrane cell surface soma neuron projection cell periphery integral component of plasma membrane Biological process chemical synaptic transmission gamma-aminobutyric acid biosynthetic process glutamate biosynthetic process neuromuscular process controlling balance response to light stimulus cell morphogenesis involved in neuron differentiation cranial nerve development response to antibiotic ion transport hearing glutamate secretion auditory behavior neurotransmitter uptake response to wounding positive regulation of synaptic transmission glutamate metabolic process L-glutamate import amino acid transport D-aspartate import across plasma membrane potassium ion transmembrane transport L-glutamate import across plasma membrane L-aspartate import across plasma membrane chloride transmembrane transport L-glutamate transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6507 20512 Ensembl ENSG00000079215 ENSMUSG00000005360 UniProt P43003 P56564 RefSeq (mRNA) NM_001166695 NM_001166696 NM_001289939 NM_001289940 NM_004172 NM_148938 RefSeq (protein) NP_001160167 NP_001160168 NP_001276868 NP_001276869 NP_004163 NP_683740 Location (UCSC) Chr 5: 36.6 – 36.69 Mb Chr 15: 8.66 – 8.74 Mb PubMed search [3] [4]
Wikidata
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EAAT1 is predominantly expressed in the plasma membrane, allowing it to remove glutamate from the extracellular space.^[6] It has also been localized in the inner mitochondrial membrane as part of the malate-aspartate shuttle.^[7]

Mechanism

EAAT1 functions in vivo as a homotrimer.^[8] EAAT1 mediates the transport of glutamic and aspartic acid with the cotransport of three Na⁺ and one H⁺ cations and counter transport of one K⁺ cation. This co-transport coupling (or symport) allows the transport of glutamate into cells against a concentration gradient.^[9]

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  "Diagram Illustrating the Malate-Aspartate Shuttle Pathway". (Glutamate aspartate transporter labeled at bottom center.)
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  Expression of SLC1A3 in the Bergmann glia fibers. Mouse brain at 7th postnatal day, sagittal section; GENSAT database.

Tissue distribution

EAAT1 is expressed throughout the CNS,^[10] and is highly expressed in astrocytes and Bergmann glia in the cerebellum.^[11][12] In the retina, EAAT1 is expressed in Muller cells.^[13] EAAT1 is also expressed in a number of other tissues including cardiac myocytes.^[7]

Clinical significance

It is associated with type 6 episodic ataxia.^[14] EAAT1 expression may also be associated with osteoarthritis.^[15]

Pharmacology

DL-threo-beta-benzyloxyaspartate (TBOA) is an inhibitor of the excitatory amino acid transporters.^[16]

Selective inhibitors for EAAT1 have recently been discovered based on 25 combinations of substitutions at the 4 and 7 positions of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitril.^[17]