ArticleThe Journal of biological chemistry2009
SNAT2 amino acid transporter is regulated by amino acids of the SLC6 gamma-aminobutyric acid transporter subfamily in neocortical neurons and may play no role in delivering glutamine for glutamatergic transmission.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Loss of TAFAZZIN leads to perturbation of amino acid metabolism and reduction of collagen synthesis.bioRxiv : the preprint server for biology · 2026Article
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- TargetingInternational journal of molecular sciences · 2024Review
- Sodium-Dependent Neutral Amino Acid Transporter 2 Can Serve as a Tertiary Carrier for l-Type Amino Acid Transporter 1-Utilizing Prodrugs.Molecular pharmaceutics · 2023Article
- Melatonin Attenuates HInternational journal of molecular sciences · 2022Article
- Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs).Pharmaceutics · 2022Review
- Article
- Physiological synaptic activity and recognition memory require astroglial glutamine.Nature communications · 2022Article
- Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease.Nature communications · 2021Article
- Glutamine Cooperatively Upregulates Lipopolysaccharide-Induced Nitric Oxide Production in BV2 Microglial Cells through the ERK and Nrf-2/HO-1 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2020Article
- Taurine Transporter Regulates Adipogenic Differentiation of Human Adipose-Derived Stem Cells through Affecting Wnt/β-catenin Signaling Pathway.International journal of biological sciences · 2019Article
- Role of C/EBP-β in Methamphetamine-Mediated Microglial Apoptosis.Frontiers in cellular neuroscience · 2019Article
- Oligodendroglioma Cells Lack Glutamine Synthetase and Are Auxotrophic for Glutamine, but Do not Depend on Glutamine Anaplerosis for Growth.International journal of molecular sciences · 2018Article
- Functional identification of activity-regulated, high-affinity glutamine transport in hippocampal neurons inhibited by riluzole.Journal of neurochemistry · 2017Article
- Disinhibition reduces extracellular glutamine and elevates extracellular glutamate in rat hippocampus in vivo.Epilepsy research · 2015Article
- Dysregulation of glutamine transporter SNAT1 in Rett syndrome microglia: a mechanism for mitochondrial dysfunction and neurotoxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Characterization and Regulation of the Amino Acid Transporter SNAT2 in the Small Intestine of Piglets.PloS one · 2015Article
- Glutamate as a neurotransmitter in the healthy brain.Journal of neural transmission (Vienna, Austria : 1996) · 2014Review
- The SLC38 family of sodium-amino acid co-transporters.Pflugers Archiv : European journal of physiology · 2014Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
System A transporters SNAT1 and SNAT2 mediate uptake of neutral alpha-amino acids (e.g. glutamine, alanine, and proline) and are expressed in central neurons. We tested the hypothesis that SNAT2 is required to support neurotransmitter glutamate synthesis by examining spontaneous excitatory activity after inducing or repressing SNAT2 expression for prolonged periods. We stimulated de novo synthesis of SNAT2 mRNA and increased SNAT2 mRNA stability and total SNAT2 protein and functional activity, whereas SNAT1 expression was unaffected. Increased endogenous SNAT2 expression did not affect spontaneous excitatory action-potential frequency over control. Long term glutamine exposure strongly repressed SNAT2 expression but increased excitatory action-potential frequency. Quantal size was not altered following SNAT2 induction or repression. These results suggest that spontaneous glutamatergic transmission in pyramidal neurons does not rely on SNAT2. To our surprise, repression of SNAT2 activity was not limited to System A substrates. Taurine, gamma-aminobutyric acid, and beta-alanine (substrates of the SLC6 gamma-aminobutyric acid transporter family) repressed SNAT2 expression more potently (10x) than did System A substrates; however, the responses to System A substrates were more rapid. Since ATF4 (activating transcription factor 4) and CCAAT/enhancer-binding protein are known to bind to an amino acid response element within the SNAT2 promoter and mediate induction of SNAT2 in peripheral cell lines, we tested whether either factor was similarly induced by amino acid deprivation in neurons. We found that glutamine and taurine repressed the induction of both transcription factors. Our data revealed that SNAT2 expression is constitutively low in neurons under physiological conditions but potently induced, together with the taurine transporter TauT, in response to depletion of neutral amino acids.
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