A shared vesicular carrier allows synaptic corelease of GABA and glycine
Open accessAbstract
The type of vesicular transporter expressed by a neuron is thought to determine its neurotransmitter phenotype. We show that inactivation of the vesicular inhibitory amino acid transporter (Viaat, VGAT) leads to embryonic lethality, an abdominal defect known as omphalocele, and a cleft palate. Loss of Viaat causes a drastic reduction of neurotransmitter release in both GABAergic and glycinergic neurons, indicating that glycinergic neurons do not express a separate vesicular glycine transporter. This loss of GABAergic and glycinergic synaptic transmission does not impair the development of inhibitory synapses or the expression of KCC2, the K+ -Cl- cotransporter known to be essential for the establishment of inhibitory neurotransmission. In the absence of Viaat, GABA-synthesizing enzymes are partially lost from presynaptic terminals. Since GABA and glycine compete for vesicular uptake, these data point to a close association of Viaat with GABA-synthesizing enzymes as a key factor in specifying GABAergic neuronal phenotypes.
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GABA and glycine compete for packaging into synaptic vesicles because both are transported by vGAT.
“Notably, GABA and glycine compete for packaging into synaptic vesicles as both are transported by the same vesicular transporter vGAT 50 (Figure 1A).”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [50]
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- Authors
- Wojcik, S. M., Katsurabayashi, S., Guillemin, I., Friauf, E., Rosenmund, C., Brose, N., & Rhee, J.-S.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- Baylor College of Medicine (US)
- University of Kaiserslautern (DE)
- Corresponding author
- Wojcik, Sonja M.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 50
- Issue
- 4
- Pages
- 575-587
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2158404383
- Cited by
- 374
- References
- 59
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 11 · 2023: 9 · 2022: 17 · 2021: 22 · 2020: 14 · 2019: 20 · 2018: 24 · 2017: 16 · 2016: 23 · 2015: 18 · 2014: 22 · 2013: 25 · 2012: 28
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2670 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (GK 845)
- Max-Planck-Gesellschaft
- Brown Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- GABA, glycine, GABAergic neurons, glycinergic neurons, embryonic lethality, omphalocele, cleft palate, KCC2, inhibitory neurotransmission, GABA synthesis, presynaptic terminals
- MeSH terms
- K Cl- Cotransporters, Animals, Brain, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Glycine, Isoenzymes, Membrane Potentials, Synaptic Transmission, Neurons, Phenotype, Spinal Cord, Synapses, Immunoblotting, Receptors, Glycine, Receptors, GABA, Mice, Knockout, Patch-Clamp Techniques, Symporters, Vesicular Inhibitory Amino Acid Transport Proteins, Mice
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