SLC1A1

Last update 08 May 2025

Basic Info

Synonyms

EAAC1, EAAT3, Excitatory amino acid transporter 3

+ [7]

Introduction

Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:21123949, PubMed:26690923, PubMed:33658209, PubMed:7521911, PubMed:7914198, PubMed:8857541). Can also transport L-cysteine (PubMed:21123949). 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 (PubMed:26690923, PubMed:33658209, PubMed:7521911, PubMed:8857541). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:26690923, PubMed:8857541). Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:21123949). 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 (By similarity). Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport (By similarity). Negatively regulated by ARL6IP5 (By similarity).

100 Clinical Results associated with SLC1A1

100 Translational Medicine associated with SLC1A1

0 Patents (Medical) associated with SLC1A1

1,014

Literatures (Medical) associated with SLC1A1

01 Jun 2025·Chemosphere

Oral exposure to nanoplastics and food allergy in mice fed a normal or high-fat diet

Article

Author: Ohno, Yuriko ; Honda, Akiko ; Saijo, Yuto ; Okamura, Takuro ; Fukui, Michiaki ; Takano, Hirohisa ; Nakanishi, Naoko ; Hamaguchi, Masahide ; Hasegawa, Yuka

The global prevalence of food allergies, particularly IgE-mediated responses, is increasing at an alarming rate. This trend is likely driven by environmental factors such as nanoplastics (NPs) ingestion and the westernization of dietary and lifestyle habits. This study examines the impact of polystyrene nanoplastics (PS-NPs) on ovalbumin (OVA)-induced food allergies in mice subjected to either a normal diet (ND) or a high-fat diet (HFD). BALB/c mice were stratified into eight groups based on dietary regimen, NP exposure, and OVA sensitization. Food allergy was induced via OVA administration, and multiple physiological and immunological parameters were evaluated, including body weight, intestinal permeability, cytokine profiles, gut microbiota composition, and small intestinal gene expression. Mice in the HFD + OVA + NP group exhibited significant increases in intestinal permeability, diarrhea severity, and serum OVA-specific IgE levels compared to other groups. Flow cytometric analysis revealed an expansion of innate lymphoid cells (ILC2 and ILC1) within the lamina propria of the small intestine. Shotgun metagenomic sequencing demonstrated gut microbiota dysbiosis, characterized by a reduction in beneficial bacterial populations in the HFD + OVA + NP cohort. Weighted Gene Co-Expression Network Analysis (WGCNA) identified a negative correlation between NPs exposure or OVA sensitization and the expression of Slc1a1, Slc5a8, and Mep1a, while a positive correlation was observed with Aa467197 expression. These findings indicate that oral exposure to PS-NPs exacerbates OVA-induced food allergies, particularly in the context of an HFD, through mechanisms involving increased intestinal permeability, gut microbial dysbiosis, and gene expression modulation. This study highlights the potential health hazards posed by environmental microplastic contamination and its possible contribution to the escalating incidence of food allergies.

01 May 2025·Biomedicine & Pharmacotherapy

EAAT3 modulation: A potential novel avenue towards remyelination in multiple sclerosis

Article

Author: Willems, Emily ; Sauer, David B ; Nouboers, Evelien ; Tiane, Assia ; Hellings, Niels ; Moya, Pablo R ; Schepers, Melissa ; Vanmierlo, Tim ; Vangansewinkel, Tim ; Rombaut, Ben ; Kumar, Vijay ; van Veggel, Lieve ; Diliën, Hanne ; Ozcan, Berra ; Noordijk, Jurrie ; Li, Anna ; Wolfs, Esther ; Schreiber, Rudy

Modulating the excitatory amino acid transporter 3 (EAAT3) can be considered a novel approach for the treatment of multiple sclerosis (MS). EAAT3 plays a crucial role in regulating oxidative stress and oligodendrocyte function through its ability to transport cysteine, the rate-limiting building block in the synthesis of the antioxidant glutathione. Therefore, EAAT3 activation is hypothesised to improve oligodendrocyte health and relieve its differentiation block in MS, improving remyelination capacity. Using a cuprizone-induced demyelination model, the effects of EAAT3 overexpression by viral transduction of oligodendrocytes and pharmacological inhibition of EAAT3 were examined. Surprisingly, EAAT3 overexpression significantly hampered remyelination, while EAAT3 inhibition prevented demyelination and improved functional remyelination as assessed by visual evoked potentials and post mortem myelin basic protein fluorescent staining. Next, cellular mechanisms underlying these results were investigated. Consistent with the in vivo findings, post mortem gene expression analysis of the corpus callosum of cuprizone treated animals revealed a trend towards upregulation of oligodendrocyte lineage genes in response to EAAT3 inhibition, supporting its role in oligodendrocyte health and myelination processes. In vitro studies using the human oligodendroglioma (HOG) cell line demonstrated the beneficial effects of EAAT3 inhibition on cellular morphology, indicating potential roles in promoting oligodendrocyte maturation and myelination. In contrast, EAAT3 overexpression appears to hamper these processes. These findings suggest that, contrary to our initial hypothesis, EAAT3 inhibition could improve oligodendrocyte function and myelination processes, highlighting its potential as a therapeutic target for demyelinating disorders. Future studies should address the exact molecular mechanism through which this effect is obtained.

22 Apr 2025·Proceedings of the National Academy of Sciences

Structural basis of excitatory amino acid transporter 3 substrate recognition

Article

Author: Qiu, Biao ; Boudker, Olga

Excitatory amino acid transporters (EAATs) reside on cell surfaces and uptake substrates, including L-glutamate, L-aspartate, and D-aspartate, using ion gradients. Among five EAATs, EAAT3 is the only isoform that can efficiently transport L-cysteine, a substrate for glutathione synthesis. Recent studies suggest that EAAT3 also transports the oncometabolite R-2-hydroxyglutarate (R-2HG). Here, we examined the structural basis of substrate recognition by determining the cryogenic electron microscopy (cryo-EM) structures of EAAT3 bound to different substrates. We found that L-cysteine binds to EAAT3 in thiolate form, and EAAT3 recognizes different substrates by fine-tuning local conformations of the coordinating residues. However, using purified human EAAT3, we could not observe R-2HG binding or transport. Imaging of EAAT3 bound to L-cysteine revealed several conformational states, including an outward-facing state with a semi-open gate and a disrupted sodium-binding site. These structures demonstrate that the full gate closure, coupled with the binding of the last sodium ion, occurs after substrate binding. Furthermore, we observed that different substrates affect how the transporter distributes between a fully outward-facing conformation and intermediate occluded states on a path to the inward-facing conformation, suggesting that translocation rates are substrate-dependent.

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SLC1A1

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