ArticleThe Journal of biological chemistry2011
A glutamine residue conserved in the neurotransmitter:sodium:symporters is essential for the interaction of chloride with the GABA transporter GAT-1.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease.The Journal of biological chemistry · 2012Trial
- A reversible allosteric inhibitor of GlyT2 for neuropathic pain without on-target side effects.Nature communications · 2026Article
- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- A reversible allosteric inhibitor of GlyT2 alleviates neuropathic pain without on-target side effects.bioRxiv : the preprint server for biology · 2025Article
- Molecular basis of human GABA transporter 3 inhibition.Nature communications · 2025Article
- Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism.Nature structural & molecular biology · 2023Article
- A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain.Frontiers in physiology · 2023Review
- The "www" ofMembranes · 2022Review
- Forty Four Years With Baruch Kanner and The Chloride Ion.Neurochemical research · 2022Article
- The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.Neurochemical research · 2022Article
- Chloride-dependent conformational changes in the GlyT1 glycine transporter.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecular Dynamic Simulations to Probe Stereoselectivity of Tiagabine Binding with Human GAT1.Molecules (Basel, Switzerland) · 2020Article
- Modeling and Simulation ofComputational and structural biotechnology journal · 2019Article
- Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective.Frontiers in chemistry · 2018Review
- Modification of a Putative Third Sodium Site in the Glycine Transporter GlyT2 Influences the Chloride Dependence of Substrate Transport.Frontiers in molecular neuroscience · 2018Article
- An Extra Amino Acid Residue in Transmembrane Domain 10 of the γ-Aminobutyric Acid (GABA) Transporter GAT-1 Is Required for Efficient Ion-coupled Transport.The Journal of biological chemistry · 2017Article
- Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog.The Journal of biological chemistry · 2016Article
- A binding mode hypothesis of tiagabine confirms liothyronine effect on γ-aminobutyric acid transporter 1 (GAT1).Journal of medicinal chemistry · 2015Article
- Conformationally sensitive proximity of extracellular loops 2 and 4 of the γ-aminobutyric acid (GABA) transporter GAT-1 inferred from paired cysteine mutagenesis.The Journal of biological chemistry · 2014Article
- The two Na+ sites in the human serotonin transporter play distinct roles in the ion coupling and electrogenicity of transport.The Journal of biological chemistry · 2014Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurotransmitter:sodium symporters are crucial for efficient synaptic transmission. The transporter GAT-1 mediates electrogenic cotransport of GABA, sodium, and chloride. The presence of chloride enables the transporter to couple the transport of the neurotransmitter to multiple sodium ions, thereby enabling its accumulation against steep concentration gradients. Here we study the functional impact of mutations of the putative chloride-binding residues on transport by GAT-1, with the emphasis on a conserved glutamine residue. In contrast to another putative chloride coordinating residue, Ser-331, where mutation to glutamate led to chloride-independent GABA transport, the Q291E mutant was devoid of any transport activity, despite substantial expression at the plasma membrane. Low but significant transport activity was observed with substitution mutants with small side chains such as Q291S/A/G. Remarkably, when these mutations were combined with the S331E mutation, transport was increased significantly, even though the activity of the S331E single mutant was only ∼25% of that of wild type GAT-1. Transport by these double mutants was largely chloride-independent. Like mutants of other putative chloride coordinating residues, the apparent affinity of the active Gln-291 single mutants for chloride was markedly reduced along with a change their anion selectivity. In addition to the interaction of the transporter with chloride, Gln-291 is also required at an additional step during transport. Electrophysiological analysis of the Q291N and Q291S mutants, expressed in Xenopus laevis oocytes, is consistent with the idea that this additional step is associated with the gating of the transporter.
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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.