2021
DOI: 10.1007/s11064-021-03252-x
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Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters

Abstract: Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After its release from presynaptic nerve terminals, glutamate is quickly removed from the synaptic cleft by excitatory amino acid transporters (EAATs) 1–5, a subfamily of glutamate transporters. The five proteins utilize a complex transport stoichiometry that couples glutamate transport to the symport of three Na+ ions and one H+ in exchange with one K+ to accumulate glutamate against up to 106-fold concentration gradie… Show more

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Cited by 15 publications
(17 citation statements)
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References 95 publications
(139 reference statements)
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“…We thus believe that the differences between these three transporters with respect to their handling of K in + represent a continuum, as opposed to divergence, in ionic coupling and kinetic decision points during substrate transport. In this context, it is worth pointing out that the family of SLC1 glutamate transporters, another important family of neurotransmitter transporters, comprises members that are categorized as either (i) K + -dependent, that is, they utilize K in + as an obligatory co-substrate or (ii) K + -independent, that is, they do not require K in + for completion of the transport cycle ( Alleva and Machtens, 2021 ). However, K in + was shown to bind to the same binding sites in both subfamilies ( Wang et al, 2019 ; Kortzak et al, 2019 ; Wang et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%
“…We thus believe that the differences between these three transporters with respect to their handling of K in + represent a continuum, as opposed to divergence, in ionic coupling and kinetic decision points during substrate transport. In this context, it is worth pointing out that the family of SLC1 glutamate transporters, another important family of neurotransmitter transporters, comprises members that are categorized as either (i) K + -dependent, that is, they utilize K in + as an obligatory co-substrate or (ii) K + -independent, that is, they do not require K in + for completion of the transport cycle ( Alleva and Machtens, 2021 ). However, K in + was shown to bind to the same binding sites in both subfamilies ( Wang et al, 2019 ; Kortzak et al, 2019 ; Wang et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%
“…ASCT1/2 have the glutamate transporter-fold (Glt), while SLC7 family transporters have the LeuT-fold [10,53]. In glutamate-type transporters a whole domain makes an elevatorlike movement across the membrane after closure of a gate formed by hairpin-loop 2 [54]. Closure of the loop triggers translocation.…”
Section: Discussionmentioning
confidence: 99%
“… 17 , 18 Excitatory amino acid transporters (EAATs) localized in astrocytes and neurons catalyze glutamate metabolism and diminish extracellular glutamate. 19 Glial EAAT1 (GLAST) and EAAT2 (GLT-1) are the most crucial of these transporters, since they are responsible for glutamate uptake throughout the brain. 19 In patients with drug-resistant temporal lobe epilepsy, the hippocampal expression levels of glial EAAT1 (GLAST) and EAAT2 (GLT-1) were shown to be decreased.…”
Section: Discussionmentioning
confidence: 99%
“… 19 Glial EAAT1 (GLAST) and EAAT2 (GLT-1) are the most crucial of these transporters, since they are responsible for glutamate uptake throughout the brain. 19 In patients with drug-resistant temporal lobe epilepsy, the hippocampal expression levels of glial EAAT1 (GLAST) and EAAT2 (GLT-1) were shown to be decreased. 17 These long-term alterations in EAAT expression indicate that EAATs may play a role in plasma glutamate abnormalities in patients with DRE.…”
Section: Discussionmentioning
confidence: 99%