ArticleThe Journal of biological chemistry2010
Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review.Frontiers in neuroscience · 2022Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Post-Translational Modifications of NTCP: A Regulatory Nexus for Bile Acid Transport and HBV Entry.Biomedicines · 2026Review
- Inhibitory Potential of the Truncated Isoforms on Glutamate Transporter Oligomerization Identified by Computational Analysis of Gene-Centric Isoform Maps.Pharmaceutical research · 2024Article
- Assaying Proliferation Characteristics of Cells Cultured Under Static Versus Periodic Conditions.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Glutamate Transporters: Expression and Function in Oligodendrocytes.Neurochemical research · 2020Article
- Proliferation characteristics of cells cultured under periodic versus static conditions.Cytotechnology · 2019Article
- Characterization of a Dopamine Transporter and Its Splice Variant Reveals Novel Features of Dopaminergic Regulation in the Honey Bee.Frontiers in physiology · 2019Article
- Troglitazone Impedes the Oligomerization of Sodium Taurocholate Cotransporting Polypeptide and Entry of Hepatitis B Virus Into Hepatocytes.Frontiers in microbiology · 2018Article
- The role of glutamate transporters in the pathophysiology of neuropsychiatric disorders.NPJ schizophrenia · 2017Review
- Role of astrocytic glutamate transporter in alcohol use disorder.World journal of psychiatry · 2016Review
- A Recombinant Human Pluripotent Stem Cell Line Stably Expressing Halide-Sensitive YFP-I152L for GABAAR and GlyR-Targeted High-Throughput Drug Screening and Toxicity Testing.Frontiers in molecular neuroscience · 2016Article
- Glutamate transporter splice variant expression in an enriched pyramidal cell population in schizophrenia.Translational psychiatry · 2015Article
- Differential regulation of two isoforms of the glial glutamate transporter EAAT2 by DLG1 and CaMKII.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Decreased EAAT2 protein expression in the essential tremor cerebellar cortex.Acta neuropathologica communications · 2014Article
- The Concise Guide to PHARMACOLOGY 2013/14: transporters.British journal of pharmacology · 2013Article
- Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1.The Journal of biological chemistry · 2013Article
- Differential expression of the glutamate transporter GLT-1 in pancreas.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glial transporter excitatory amino acid transporter-2 (EAAT2) is the main mediator of glutamate clearance in brain. The wild-type transporter (EAAT2wt) forms trimeric membrane complexes in which each protomer functions autonomously. Several EAAT2 variants are found in control and Alzheimer-diseased human brains; their expression increases with pathological severity. These variants might alter EAAT2wt-mediated transport by abrogating membrane trafficking, or by changing the configuration or functionality of the assembled transporter complex. HEK293 cells were transfected with EAAT2wt; EAAT2b, a C-terminal variant; or either of two exon-skipping variants: alone or in combination. Surface biotinylation studies showed that only the exon-7 deletion variant was not trafficked to the membrane when transfected alone, and that all variants could reach the membrane when co-transfected with EAAT2wt. Fluorescence resonance energy transfer (FRET) studies showed that co-transfected EAAT2wt and EAAT2 splice variants were expressed in close proximity. Glutamate transporter function was measured using a whole cell patch clamp technique, or by changes in membrane potential indexed by a voltage-sensitive fluorescent dye (FMP assay): the two methods gave comparable results. Cells transfected with EAAT2wt or EAAT2b showed glutamate-dependent membrane potential changes consistent with functional expression. Cells transfected with EAAT2 exon-skipping variants alone gave no response to glutamate. Co-transfection of EAAT2wt (or EAAT2b) and splice variants in various ratios significantly raised glutamate EC(50) and decreased Hill coefficients. We conclude that exon-skipping variants form heteromeric complexes with EAAT2wt or EAAT2b that traffic to the membrane but show reduced glutamate-dependent activity. This could allow glutamate to accumulate extracellularly and promote excitotoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.