ArticleEMBO molecular medicine2021
SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Uptake of L-proline by Cultured Primary Rat Astrocytes.Neurochemical research · 2026Article
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Deep neural networks and genome-wide associations reveal the polygenic architecture of local brain aging.GeroScience · 2026Article
- Glycine-modulating Slc6a20a-ASO restores NMDA receptor function in SHANK2 and SHANK3-mutant mice and cortical organoids.Nature communications · 2026Article
- Genetic variations interact with polybrominated diphenyl ether exposure to alter lipid homeostasis.Nature communications · 2026Article
- The NMDAR/TRPM4 death complex is a major promoter of disease progression in the 5xFAD mouse model of Alzheimer's disease.Molecular psychiatry · 2026Article
- Dietary folic acid prevents peripheral neuropathy in mouse models of neural tube defects and type 2 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Novel binding mode for negative allosteric NMDA receptor modulators.The Journal of general physiology · 2026Article
- A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.Journal of inherited metabolic disease · 2026Article
- Molecular and cellular mechanisms underlying gyrate atrophy: Why is the retina primarily affected?Acta ophthalmologica · 2025Review
- Metabolite classification through novel metabolomics framework reveals mechanism underlying the therapeutic effects of PSD95-nNOS blockade for post-stroke depression.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Exploring the Association Between Human Blood Metabolites and Autism Spectrum Disorder Risk: A Bidirectional Mendelian Randomization Study.Health science reports · 2025Article
- Design of (Journal of medicinal chemistry · 2025Article
- Evaluation of allosteric N-methyl-d-aspartate receptor modulation by GluN2A-selective antagonists using pharmacological equilibrium modeling.Molecular pharmacology · 2025Article
- Role of the Neanderthal Genome in Genetic Susceptibility to COVID-19: 3p21.31 Locus in the Spotlight.Biochemical genetics · 2024Review
- Single-nucleus RNA sequencing-based construction of a hippocampal neuron atlas in mice with epileptic cognitive impairment.iScience · 2024Article
- Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2.Nature communications · 2024Article
- Alcohol Consumption Is a Coping Mechanism for Male Patients with Severe Anxiety Disorders Treated with Antidepressants Monotherapy.Journal of clinical medicine · 2024Article
- Proteomic alterations in the brain and blood-brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer's disease.Fluids and barriers of the CNS · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co-agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β-catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide-induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction.
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