ArticleBiochemistry2005
Individual subunits of the glutamate transporter EAAC1 homotrimer function independently of each other.
Article in Biochemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 145 citations in OpenAlex.
- Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism.The EMBO journal · 2026Article
- Evolutionary analysis reveals the origin of sodium coupling in glutamate transporters.Nature structural & molecular biology · 2025Article
- The severity of SLC1A2-associated neurodevelopmental disorders correlates with transporter dysfunction.EBioMedicine · 2025Article
- Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.Nature communications · 2024Article
- Symport and antiport mechanisms of human glutamate transporters.Nature communications · 2023Article
- Structural basis of ligand binding modes of human EAAT2.Nature communications · 2022Article
- The archaeal glutamate transporter homologue GltPh shows heterogeneous substrate binding.The Journal of general physiology · 2022Article
- The ion-coupling mechanism of human excitatory amino acid transporters.The EMBO journal · 2022Article
- Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters.Neurochemical research · 2022Review
- Pre-Steady-State Kinetics and Reverse Transport in Rat Glutamate Transporter EAAC1 with an Immobilized Transport Domain.Neurochemical research · 2022Article
- Kinetic mechanism of NaCommunications biology · 2021Article
- Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.Science advances · 2021Article
- Observing spontaneous, accelerated substrate binding in molecular dynamics simulations of glutamate transporters.PloS one · 2021Article
- Cellular Physiology and Pathophysiology of EAAT Anion Channels.Frontiers in cellular neuroscience · 2021Review
- Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression.Frontiers in cellular neuroscience · 2021Review
- Saturation transfer difference NMR on the integral trimeric membrane transport protein GltPh determines cooperative substrate binding.Scientific reports · 2020Article
- Elevator-type mechanisms of membrane transport.Biochemical Society transactions · 2020Review
- Amino Acid Transporters and Exchangers from the SLC1A Family: Structure, Mechanism and Roles in Physiology and Cancer.Neurochemical research · 2020Review
- Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment.Nature communications · 2020Article
- Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Glutamate transporters are thought to be assembled as trimers of identical subunits that line a central hole, possibly the permeation pathway for anions. Here, we have tested the effect of multimerization on the transporter function. To do so, we coexpressed EAAC1(WT) with the mutant transporter EAAC1(R446Q), which transports glutamine but not glutamate. Application of 50 microM glutamate or 50 microM glutamine to cells coexpressing similar numbers of both transporters resulted in anion currents of 165 and 130 pA, respectively. Application of both substrates at the same time generated an anion current of 297 pA, demonstrating that the currents catalyzed by the wild-type and mutant transporter subunits are purely additive. This result is unexpected for anion permeation through a central pore but could be explained by anion permeation through independently functioning subunits. To further test the subunit independence, we coexpressed EAAC1(WT) and EAAC1(H295K), a transporter with a 90-fold reduced glutamate affinity as compared to EAAC1(WT), and determined the glutamate concentration dependence of currents of the mixed transporter population. The data were consistent with two independent populations of transporters with apparent glutamate affinities similar to those of EAAC1(H295K) and EAAC1(WT), respectively. Finally, we coexpressed EAAC1(WT) with the pH-independent mutant transporter EAAC1(E373Q), showing two independent populations of transporters, one being pH-dependent and the other being pH-independent. In conclusion, we propose that EAAC1 assembles as trimers of identical subunits but that the individual subunits in the trimer function independently of each other.
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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.