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Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate. Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion. Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport. Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate.
基因功能參考文獻(xiàn):
EAAT1 rs2731880 SNP is associated with amygdala functional connectivity in bipolar disorder. PMID: 30073554
Episodic ataxias 6 is caused by heterozygous mutations in SLC1A3, which encodes a subunit of a glial excitatory amino acid transporter, EAAT1. PMID: 29891059
a novel missense mutation, c.383T>G (p.Met128Arg) in SLC1A3, in an episodic ataxia patient by whole-exome sequencing. PMID: 29208948
This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. PMID: 27476799
crystal structures of a thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1 (EAAT1), with and without allosteric and competitive inhibitors bound PMID: 28424515
This study demonstrated that the cytopathology and episodic paralysis in our Drosophila EA6 model stem from a gain-of-function chloride channelopathy of glial cells.. PMID: 27445142
Starvation of Muller cells increased the glutamate uptake capacity as well as the expression of the most abundant glutamate transporter, EAAT1. PMID: 27196320
A heterozygous SLC1A3 c.1177G4A mutation has been detected in a patient with late-onset episodic ataxia. Same heterozygous mutation was identified in one clinically affected family member and two asymptomatic members. PMID: 27829685
We consider an association between SLC1A3 and the behavioural problems which can also be considered a contributing factor to behavioural problems in larger duplications overlapping the 5p13 microduplication syndrome region. PMID: 27296938
In combination with other nearby residues, Arg-388 coordinates anion channel gating and forms part of the missing structural link between the anion conducting and substrate transport states in EAAT1. PMID: 26683197
There was no association between pyramidal cell EAAT1 splice variant expression and schizophrenia. PMID: 26057049
data provide additional insights into the mechanism by which substrates gate the anion conductance in EAATs and suggest that in EAAT1, Arg-388 is a critical element for the structural coupling between the substrate translocation and the gating mechanisms PMID: 26203187
discovering compounds that can enhance EAAT1 expression and activity may be a novel strategy for therapeutic treatment of glaucoma. PMID: 25789968
EAAT1 polymorphism which is involved in the Regulation of extracellular glutamate concentrations, influences Cognitive performances with a detrimental effect of T/T homozygosis. PMID: 25660734
Its dysregulation may contribute to the pathology and possibly affect the onset of fragile X-associated tremor/ataxia syndrome. PMID: 24332449
Increased SLC1A3 expression in the cerebellum of elderly schizophrenia patients indicates facilitated transport and may result in reduced glutamate neurotransmission. PMID: 22424243
Plasma membrane EAAT1 (and NCX1)are both involved in glutamate-induced ATP synthesis. PMID: 23913256
Decreased expression of EAAT1 protein remodels glutamate neurotransmission in the superior temporal gyrus in schizophrenia. PMID: 23356950
Episodic ataxia type 6 represents the first human disease found to be associated with altered function of excitatory amino acid transporter anion channels. PMID: 23107647
Close functional similarities of the GLAST/EAAT-1 promoter regions in man and rat exist which point to a species-specific function of the GLAST/EAAT-1 3'-UTR in constitutive and regulated GLAST/EAAT-1 expression. PMID: 22252783
EAAT-1 expression was found in 91% of choroid plexus tumors and was absent in endolymphatic sac tumors. PMID: 22706862
Letter: report expression of dishevelled-3 and EAAT1 and glutamine metabolism in malignant pleural mesothelioma. PMID: 22569537
The accessibility in the external part of the TM5 of the glutamate transporter EAAT1 is conformationally sensitive during the transport cycle. PMID: 22292083
These results indicate that E219D is a functional SLC1A3 variant that is presented in a small number of individuals with Tourette syndrome. PMID: 21233784
water and urea permeation properties of wild-type EAAT1 and two mutant transporters were measured to identify which permeation pathway facilitates the movement of these molecules PMID: 21732909
A series of single cysteine substitutions in the helical hairpin HP2 of excitatory amino acid transporter 1 form intersubunit disulfide cross-links within the trimer. PMID: 21876140
There is no association between SLC1A3 and normal tension glaucoma (NTG), suggesting that the SLC1A3 gene may not be an associated factor in NTG pathogenesis. PMID: 21528001
Dose-dependent modulation of EAAT1-mediated aspartate transport by benzodiazepines suggests a role of glial as well as neuronal transporters in drug action. PMID: 11792462
EAAT1 was strongly expressed in a subset of cortical pyramidal neurons in dementia cases showing Alzheimer-type pathology. In addition, tau (which is a marker of neurofibrillary pathology) colocalized to those same pyramidal cells that expressed EAAT1 PMID: 11826152
Data show that excitatory amino acid transporter (EAAT)-1 was expressed by activated macrophages/microglia in all HIV-infected cases but not in HIV-negative controls. PMID: 12769187
To test whether Nedd4-2, SGK1, SGK3 and protein kinase B regulate EAAT1, cRNA encoding EAAT1 was injected into Xenopus oocytes with or without injection of Nedd4-2, constitutively active[CA] S422DSGK1, inactive K127NSGK1, SGK3 and/or CA T308D,S473DPKB PMID: 12911626
Transcriptional regulation of human excitatory amino acid transporter 1 (EAAT1): cloning of the EAAT1 promoter and characterization of its basal and inducible activity in human astrocytes. PMID: 14713304
We observed decreased glutamate uptake V(max), without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction. PMID: 14749132
Only activated macrophages/microglia (AMM) expressed EAAT-1. Proportion of AMM expressing EAAT-1 did not correlate with severity of neuronal apoptosis, spongiosis, astrocytosis, microgliosis, or PrP deposition, but only with disease duration. PMID: 15535133
EAAT1 parameters were mutually correlated (p<0.01) and correlations were shown with dementia severity (p<0.05 MMSE-expression, p<0.005 MMSE-mRNA). PMID: 15718040
Genetic variation in SLC1A3 may contribute to susceptibility to ADHD. PMID: 15950021
EAAT1ex9skip splice variant is a negative regulator of full-length EAAT1 function in the human brain PMID: 16042756
Our data show that a heterozygous mutation in EAAT1 can lead to decreased glutamate uptake, which can contribute to neuronal hyperexcitability to cause seizures, hemiplegia, and episodic ataxia. PMID: 16116111
the activity of glutamate transporter GLAST/EAAT1 can effectively regulate the cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes PMID: 16516348
Rearrangements in the tertiary structure of the EAAT1 translocation pore during transport provide constraints for modeling the structural dynamics associated with transport. PMID: 16877378
SLC1A3 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population. PMID: 17221839
Activity of GLAST directs FXYD2 protein/gamma subunit to the cell surface, that leads to the activation of the astroglial sodium pump. PMID: 17316900
Continued expression of GLAST by neural progenitor cells in the transgenic mouse brain raises the possibility that GLAST may have an unanticipated role in regulating their behavior. PMID: 17581948
We documented for the first time the expression of the mGluR5 and EAAT1 in MG-63 cells, as well as the ability of dexamethasone to upregulate the expression of the mGluR5 and EAAT1 in the MG-63 cells. PMID: 17627080
Mutations in transmembrane domains 5 and 7 of the human excitatory amino acid transporter 1 affect the substrate-activated anion channel PMID: 17676873
No pathogenic mutation were identified in SLC1A3. PMID: 18446307
increased expression in the prefrontal cortex of chronic alcoholics PMID: 18657127
analysis of the importance of Leu-303 or its counterpart Leu-391 in human EAAT1 (hEAAT1) PMID: 18678877
We broadened the clinical spectrum associated with SLC1A3 mutations to include milder manifestations of EA without seizures or alternating hemiplegia. The severity of EA6 symptoms is related to the extent of glutamate transporter dysfunction. PMID: 19139306
Detected in brain. Detected at very much lower levels in heart, lung, placenta and skeletal muscle. Highly expressed in cerebellum, but also found in frontal cortex, hippocampus and basal ganglia.