Cited by 450Amino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology ResearchIon Transport and Channel Regulation

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The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects

Kanai, Yoshikatsu, Hediger, Matthias A.·2004·Pfl�gers Archiv European Journal of Physiology

DOI 10.1007/s00424-003-1146-4

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Abstract

The solute carrier family 1 (SLC1) includes five high-affinity glutamate transporters, EAAC1, GLT-1, GLAST, EAAT4 and EAAT5 (SLC1A1, SLC1A2, SLC1A3, SLC1A6, and SLC1A7, respectively) as well as the two neutral amino acid transporters, ASCT1 and ASCT2 (SLC1A4 and ALC1A5, respectively). Although each of these transporters have similar predicted structures, they exhibit distinct functional properties which are variations of a common transport mechanism. The high-affinity glutamate transporters mediate transport of l-Glu, l-Asp and d-Asp, accompanied by the cotransport of 3 Na(+) and 1 H(+), and the countertransport of 1 K(+), whereas ASC transporters mediate Na(+)-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr. The unique coupling of the glutamate transporters allows uphill transport of glutamate into cells against a concentration gradient. This feature plays a crucial role in protecting neurons against glutamate excitotoxicity in the central nervous system. During pathological conditions, such as brain ischemia (e.g. after a stroke), however, glutamate exit can occur due to "reversed glutamate transport", which is caused by a reversal of the electrochemical gradients of the coupling ions. Selective inhibition of the neuronal glutamate transporter EAAC1 (SLC1A1) may be of therapeutic interest to block glutamate release from neurons during ischemia. On the other hand, upregulation of the glial glutamate transporter GLT1 (SLC1A2) may help protect mot…

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Background
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Background
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Background
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Influential
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Background
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Background
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Background
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Background
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“Analogously to Glttk, it is plausible to assume that Na+ is coordinated at Na3 by (1) the hydroxyl group of T124 and T125, (2) the carboxamide of N378, (3) the side-chain carboxyl of D380, and (4) the lateral chain of F121 (Fig.”
Background
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“…conditions of energy deprivation, hypoxia, hypoglycaemia, brain trauma, stroke, etc., underlying an increase in the ambient glutamate concentration and development of excitotoxicity (Jabaudon et al. 1999; Kanai and Hediger 2004; Borisova and Krisanova 2008; Grewer et al. 2008; Kanai et al. 2013).”
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“These genes encode Naþ, Hþ-glutamate co-transporters (members 1e3) and the two neutral Naþ-dependent antiporters (members 4 and 5) [31].”
Background
Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1
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“Spliced variants for GLT-1 have been reported in some research [16,23,24], the expression of which is mutated in the brains of mice subjected to chemical hypoxia.”
Background
Regulation of Glial Glutamate Transporters by C-terminal Domains*
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Reconstitution into liposomes of the glutamine/amino acid transporter from renal cell plasma membrane: functional characterization, kinetics and activation by nucleotides.
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“In addition, the source of the reconstituted transporter corresponds with the cellular localization of ASCT2 in the apical plasma membrane of kidney, among other tissues [5,10,25].”
Background
Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus
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“Whereas xCT regulates the transport of cystine into cells, the alanine-serine-cysteine transporter 2 (ASCT2) regulates the transport of glutamine, cysteine, and a few other neutral amino acids into cells (27, 31).”
Background
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BackgroundInfluential
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Clinical associations between ASCT2 and p‑mTOR in the pathogenesis and prognosis of epithelial ovarian cancer.
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“ASCT2 regulates the uptake of amino acids, including glutamine (15,16).”
Background
The Role of Glutamate and the Immune System in Organophosphate-induced CNS Damage
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Background
OCDB: a database collecting genes, miRNAs and drugs for obsessive-compulsive disorder
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Background
ASCT2 is a major contributor to serine uptake in cancer cells
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The Involvement of Long Non-Coding RNAs in Glutamine-Metabolic Reprogramming and Therapeutic Resistance in Cancer
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Background
SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism
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Method
CHAPTER 65 – Protein Digestion and Absorption
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Authors: Kanai, Y., & Hediger, M. A.
Affiliations: Kyorin University (JP)
Brigham and Women's Hospital (US)
Corresponding author: Hediger, Matthias A.
ORCID: Kanai, Yoshikatsu
Hediger, Matthias A.
Venue: Pfl�gers Archiv European Journal of Physiology
Publisher: Springer Science and Business Media LLC
Published: 2004-02-01
Volume: 447
Issue: 5
Pages: 469-479
ISSN: 0031-6768 (ISSN-L)
1432-2013
DOI: 10.1007/s00424-003-1146-4
OpenAlex: W1998475753
Cited by: 450
References: 0
Citations by year: 2026: 8 · 2025: 11 · 2024: 13 · 2023: 11 · 2022: 16 · 2021: 20 · 2020: 18 · 2019: 26 · 2018: 10 · 2017: 18 · 2016: 18 · 2015: 15 · 2014: 24 · 2013: 33 · 2012: 29
FWCI: 10.30
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Pflügers Archiv - European Journal of Physiology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords: glutamate transporters, neutral amino acid transporter, EAAC1, GLT-1, GLAST, EAAT4, ASCT1, ASCT2, glutamate excitotoxicity, cerebral ischemia, glutamate release, amyotrophic lateral sclerosis, motor neuron protection
MeSH terms: Animals, Biological Transport, Multigene Family, Humans, Glutamic Acid, Amino Acids, Neutral, Amino Acid Transport System X-AG

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The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects

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