ArticleBiophysical journal2014
The domain interface of the human glutamate transporter EAAT1 mediates chloride permeation.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.Brain : a journal of neurology · 2024Article
- Symport and antiport mechanisms of human glutamate transporters.Nature communications · 2023Article
- Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6.Nature communications · 2023Article
- Molecular insights into disease-associated glutamate transporter (EAAT1 /Frontiers in molecular biosciences · 2023Article
- Ataxia-linked SLC1A3 mutations alter EAAT1 chloride channel activity and glial regulation of CNS function.The Journal of clinical investigation · 2022Article
- Article
- 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
- The mechanism and regulation of vesicular glutamate transport: Coordination with the synaptic vesicle cycle.Biochimica et biophysica acta. Biomembranes · 2020Review
- An amino-terminal point mutation increases EAAT2 anion currents without affecting glutamate transport rates.The Journal of biological chemistry · 2020Article
- Amino Acid Transporters and Exchangers from the SLC1A Family: Structure, Mechanism and Roles in Physiology and Cancer.Neurochemical research · 2020Review
- A KThe Journal of biological chemistry · 2019Article
- Article
- Substrate transport and anion permeation proceed through distinct pathways in glutamate transporters.eLife · 2017Article
- Glial and Neuronal Glutamate Transporters Differ in the NaFrontiers in molecular neuroscience · 2017Article
- Disruption of an EAAT-Mediated Chloride Channel in a Drosophila Model of Ataxia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Tuning the ion selectivity of glutamate transporter-associated uncoupled conductances.The Journal of general physiology · 2016Article
- Electrogenic Steps Associated with Substrate Binding to the Neuronal Glutamate Transporter EAAC1.The Journal of biological chemistry · 2016Article
- The Split Personality of Glutamate Transporters: A Chloride Channel and a Transporter.Neurochemical research · 2016Article
- Molecular physiology of EAAT anion channels.Pflugers Archiv : European journal of physiology · 2016Review
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3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The concentration of glutamate within the glutamatergic synapse is tightly regulated by the excitatory amino-acid transporters (EAATs). In addition to their primary role of clearing extracellular glutamate, the EAATs also possess a thermodynamically uncoupled Cl(-) conductance. Several crystal structures of an archaeal EAAT homolog, GltPh, at different stages of the transport cycle have been solved. In a recent structure, an aqueous cavity located at the interface of the transport and trimerization domains has been identified. This cavity is lined by polar residues, several of which have been implicated in Cl(-) permeation. We hypothesize that this cavity opens during the transport cycle to form the Cl(-) channel. Residues lining this cavity in EAAT1, including Ser-366, Leu-369, Phe-373, Arg-388, Pro-392, and Thr-396, were mutated to small hydrophobic residues. Wild-type and mutant transporters were expressed in Xenopus laevis oocytes and two-electrode voltage-clamp electrophysiology, and radiolabeled substrate uptake was used to investigate function. Significant alterations in substrate-activated Cl(-) conductance were observed for several mutant transporters. These alterations support the hypothesis that this aqueous cavity at the interface of the transport and trimerization domains is a partially formed Cl(-) channel, which opens to form a pore through which Cl(-) ions pass. This study enhances our understanding as to how glutamate transporters function as both amino-acid transporters and Cl(-) channels.
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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.