ArticleThe Journal of general physiology2020
Mechanism and potential sites of potassium interaction with glutamate transporters.
Article in The Journal of general physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism.The EMBO journal · 2026Article
- Extracellular KNature communications · 2026Article
- The Charge of the Substrate Determines Sodium-Coupling Stoichiometry of the Amino Acid Transporter SLC6A14.Biochemistry · 2025Article
- Symport and antiport mechanisms of human glutamate transporters.Nature communications · 2023Article
- Article
- Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19.International journal of molecular sciences · 2022Review
- Functional and Kinetic Comparison of Alanine Cysteine Serine Transporters ASCT1 and ASCT2.Biomolecules · 2022Article
- The ion-coupling mechanism of human excitatory amino acid transporters.The EMBO journal · 2022Article
- Modeling of SGLT1 in Reconstituted Systems Reveals Apparent Ion-Dependencies of Glucose Uptake and Strengthens the Notion of Water-Permeable Apo States.Frontiers in physiology · 2022Article
- Pre-Steady-State Kinetics and Reverse Transport in Rat Glutamate Transporter EAAC1 with an Immobilized Transport Domain.Neurochemical research · 2022Article
- Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters.Neurochemical research · 2022Review
- Handling of intracellular KeLife · 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
- Pre-steady-state Kinetic Analysis of Amino Acid Transporter SLC6A14 Reveals Rapid Turnover Rate and Substrate Translocation.Frontiers in physiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In the mammalian glutamate transporters, countertransported intracellular K+ is essential for relocating the glutamate binding site to the extracellular side of the membrane. This K+-dependent process is believed to be rate limiting for the transport cycle. In contrast, extracellular K+ induces glutamate release upon transporter reversal. Here, we analyzed potential K+ binding sites using molecular dynamics (MD) simulations and site-directed mutagenesis. Two candidate sites were identified by spontaneous K+ binding in MD simulations, one site (K1 site) overlapping with the Na1 Na+ binding site and the K2 site being localized under hairpin loop 2 (HP2). Mutations to conserved amino acid residues in these sites resulted in several transporters that were defective in K+-induced reverse transport and which bound K+ with reduced apparent affinity compared with the wild-type transporter. However, external K+ interaction was abolished in only one mutant transporter EAAC1D454A in the K1 site. Our results, for the first time, directly demonstrate effects of K1-site mutations on K+ binding, in contrast to previous reports on K+ binding sites based on indirect evidence. We propose that K+ binding to the K1 site is responsible for catalyzing the relocation step, whereas binding to the K2 site may have an as-of-yet unidentified regulatory function.
Indexed as
Identifiers
What OpenQuestion holds
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.