ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
The glycine transporter GlyT2 controls the dynamics of synaptic vesicle refilling in inhibitory spinal cord neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease.The Journal of biological chemistry · 2012Trial
- The sympathoregulatory region of the mouse rostral brainstem relies on both GABA and glycine to generate inhibitory currents.The Journal of physiology · 2026Article
- Dysmorphic neurons express markers of inhibitory glycinergic signaling in focal cortical dysplasia IIb.Brain pathology (Zurich, Switzerland) · 2026Article
- Slc6a9 is distributed in glial cells and neurons across several nervous system regions, whereas Slc6a5 is more restricted to neurons in the caudal brain.BMC neuroscience · 2026Article
- A reversible allosteric inhibitor of GlyT2 for neuropathic pain without on-target side effects.Nature communications · 2026Article
- Spinal glycine receptor alpha 1 coordinates startle behavior through a cell-type specific mechanism.International journal of biological sciences · 2026Article
- A reversible allosteric inhibitor of GlyT2 alleviates neuropathic pain without on-target side effects.bioRxiv : the preprint server for biology · 2025Article
- Synaptic imbalance and increased inhibition impair motor function in SMA.Science advances · 2025Article
- Robust inhibitory glycinergic transmission and the effect of bafilomycin, folimycin and EIPA: lessons from the auditory brainstem.Frontiers in cellular neuroscience · 2025Article
- Synaptic Targets of Glycinergic Neurons in Laminae I-III of the Spinal Dorsal Horn.International journal of molecular sciences · 2023Article
- Flux coupling, not specificity, shapes the transport and phylogeny of SLC6 glycine transporters.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification of amacrine neurons with a glycinergic and GABAergic phenotype in the mouse retina.Medical research archives · 2022Article
- Neurotransmitter content heterogeneity within an interneuron class shapes inhibitory transmission at a central synapse.Frontiers in cellular neuroscience · 2022Article
- The presynaptic glycine transporter GlyT2 is regulated by the Hedgehog pathway in vitro and in vivo.Communications biology · 2021Article
- Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling.Biomolecules · 2021Review
- Structural Determinants of the Neuronal Glycine Transporter 2 for the Selective Inhibitors ALX1393 and ORG25543.ACS chemical neuroscience · 2021Article
- Neurochemistry of the Kölliker-Fuse nucleus from a respiratory perspective.Journal of neurochemistry · 2021Review
- A System for Assessing Dual Action Modulators of Glycine Transporters and Glycine Receptors.Biomolecules · 2020Article
- Glycinergic Transmission in the Presence and Absence of Functional GlyT2: Lessons From the Auditory Brainstem.Frontiers in synaptic neuroscience · 2020Article
- Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia.Frontiers in psychiatry · 2020Review
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3 authors.
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Abstract
At inhibitory synapses, glycine and GABA are accumulated into synaptic vesicles by the same vesicular transporter VGAT/VIAAT (vesicular GABA transporter/vesicular inhibitory amino acid transporter), enabling a continuum of glycine, GABA, and mixed phenotypes. Many fundamental aspects of the presynaptic contribution to the inhibitory phenotypes remain unclear. The neuronal transporter GlyT2 is one of the critical presynaptic factors, because glycinergic transmission is impaired in knock-out GlyT2(-/-) mice and mutations in the human GlyT2 gene slc6a5 are sufficient to cause hyperekplexia. Here, we establish that GlyT2-mediated uptake is directly coupled to the accumulation of glycine into recycling synaptic vesicles using cultured spinal cord neurons derived from GlyT2-enhanced green fluorescent protein transgenic mice. Membrane expression of GlyT2 was confirmed by recording glycine-evoked transporter current. We show that GlyT2 inhibition induces a switch from a predominantly glycine to a predominantly GABA phenotype. This effect was mediated by a reduction of glycinergic quantal size after cytosolic depletion of glycine and was entirely reversed by glycine resupply, illustrating that the filling of empty synaptic vesicles is tightly coupled to GlyT2-mediated uptake. Interestingly, high-frequency trains of stimuli elicit two phases of vesicle release with distinct kinetic requirements for glycine refilling. Thus, our results demonstrate the central role played by GlyT2 in determining inhibitory phenotype and therefore in the physiology and pathology of inhibitory circuits.
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