Glycine transporters and synaptic function
Open accessAbstract
Glycine is an inhibitory neurotransmitter that is mainly active in the caudal areas of the CNS. However, glycine also participates in excitatory neurotransmission since it is a co‐agonist of the NMDA subtype of glutamate receptors. The concentration of glycine at synapses is mainly controlled by two sodium and chloride dependent transporters, GLYT1 and GLYT2, proteins that display a complementary distribution and activity in the nervous system. Our understanding of the physiological role of these transporters has advanced recently, thanks to the development of specific inhibitors and the generation of mice defective in the corresponding genes. In addition, the three‐dimensional resolution of the structure of a bacterial homologue has shed light on the mechanisms of glycine transport. It is likely that this knowledge will prove to be useful for the development of drugs with antipsychotic, procognitive or analgesic properties. © 2008 IUBMB IUBMB Life, 60(12): 810–817, 2008
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The amino acids cysteine and glycine liberated by hydrolysis are efficiently taken up by sodium-dependent transporters into neurons and can be used as substrates for neuronal GSH synthesis.
“The amino acids liberated by the hydrolysis, cysteine and glycine, are efficiently taken up by sodium‐dependent transporters into neurons (Aoyama and Nakaki 2013; Zafra and Giménez 2008) and can be used as substrates for neuronal GSH synthesis (Dringen, Pfeiffer, et al. 1999; Kranich et al. 1996).”
From Glutathione Metabolism of the Brain—The Role of Astrocytes (2025) · cites this paper as Zafra and Giménez 2008
The ‘Plasma Membrane Glycine Transporters: Distribution and Function’ section describes sodium-coupled glycine transport and glycine accumulation in neurons expressing GLYT2. It does not establish neuronal uptake of cysteine or identify hydrolysis as the source of the transported glycine. The GSH-synthesis clause is attributed to different citations in the citing sentence, not to this paper. (LLM, conf=0.88)
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Cites
Identification of Tbr-1/CASK complex target genes in neurons
Wang, T., Ding, C., Wang, G., Luo, S., Lin, Y., Ruan, Y., Hevner, R., Rubenstein, J. L. R., & Hsueh, Y. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02845.x · Cited by 83 · see citing works
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- Boulland, J. L., Jenstad, M., Boekel, A. J., Wouterlood, F. G., Edwards, R. H., Storm-Mathisen, J., and Chaudhry, F. A. Vesicular glutamate and GABA transporters sort to distinct sets of vesicles in a population of presynaptic terminals. Cereb. Cortex., in press; Doi: 10.1093/cercor/ bhn077. · DOI · Paper page
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Glycine transport inhibitors in the treatment of schizophrenia
Javitt, D. C. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25758-2_12 · Cited by 83 · see citing works
Glutathione Metabolism of the Brain—The Role of Astrocytes
Dringen, R., & Arend, C. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70073 · Cited by 46 · see citing works
- Authors
- Zafra, F., & Giménez, C.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Zafra, Francisco
- Venue
- IUBMB Life
- Publisher
- Wiley
- Published
- 2008-09-17
- Volume
- 60
- Issue
- 12
- Pages
- 810-817
- ISSN
- 1521-6543 (ISSN-L)
- 1521-6551
- OpenAlex
- W1989524951
- Cited by
- 73
- References
- 1
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 6
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- IUBMB Life (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- glycine transporter, glycine transporter 1, glycine transporter 2, glycine, synaptic function, inhibitory neurotransmission, NMDA receptor co-agonist, excitatory neurotransmission, sodium-dependent transport, chloride-dependent transport, transporter structure, transporter inhibitors, knockout mice, antipsychotic drugs, analgesics
- MeSH terms
- Animals, Glycine, Humans, Nervous System Diseases, Synaptic Transmission, Glycine Plasma Membrane Transport Proteins
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