A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons
Open accessAbstract
Two proteins previously known as Na(+)-dependent phosphate transporters have been identified recently as vesicular glutamate transporters (VGLUT1 and VGLUT2). Together, VGLUT1 and VGLUT2 are operating at most central glutamatergic synapses. In this study, we characterized a third vesicular glutamate transporter (VGLUT3), highly homologous to VGLUT1 and VGLUT2. Vesicles isolated from endocrine cells expressing recombinant VGLUT3 accumulated l-glutamate with bioenergetic and pharmacological characteristics similar, but not identical, to those displayed by the type-1 and type-2 isoforms. Interestingly, the distribution of VGLUT3 mRNA was restricted to a small number of neurons scattered in the striatum, hippocampus, cerebral cortex, and raphe nuclei, in contrast to VGLUT1 and VGLUT2 transcripts, which are massively expressed in cortical and deep structures of the brain, respectively. At the ultrastructural level, VGLUT3 immunoreactivity was concentrated over synaptic vesicle clusters present in nerve endings forming asymmetrical as well as symmetrical synapses. Finally, VGLUT3-positive neurons of the striatum and raphe nuclei were shown to coexpress acetylcholine and serotonin transporters, respectively. Our study reveals a novel class of glutamatergic nerve terminals and suggests that cholinergic striatal interneurons and serotoninergic neurons from the brainstem may store and release glutamate.
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About 60% of DR serotonin neurons co-express the vesicular glutamate transporter Vglut3 in the rat and co-release glutamate in the mouse.
“~60% of DR serotonin neurons co-express the vesicular glutamate transporter Vglut3 in the rat (Gras et al., 2002) and co-release glutamate in the mouse (Liu et al., 2014; Sengupta et al., 2017).”
From Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems (2018) · cites this paper as Gras et al., 2002
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- Authors
- Gras, C., Herzog, E., Bellenchi, G. C., Bernard, V., Ravassard, P., Pohl, M., Gasnier, B., Giros, B., & El Mestikawy, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-07-01
- Volume
- 22
- Issue
- 13
- Pages
- 5442-5451
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758212
- OpenAlex
- W1630907922
- Cited by
- 639
- References
- 47
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 15 · 2023: 15 · 2022: 15 · 2021: 18 · 2020: 24 · 2019: 28 · 2018: 17 · 2017: 25 · 2016: 28 · 2015: 23 · 2014: 21 · 2013: 29 · 2012: 20
- FWCI
- 14.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- VGLUT3, VGLUT1, VGLUT2, synaptic vesicles, cholinergic neurons, serotonergic neurons, striatum, raphe nuclei, vesicular acetylcholine transporter, serotonin transporter, glutamate release, mRNA distribution
- MeSH terms
- Acetylcholine, Amino Acid Sequence, Animals, Brain, Carrier Proteins, Cell Line, Cloning, Molecular, Kinetics, Molecular Sequence Data, Neurons, Raphe Nuclei, RNA, Messenger, Serotonin, Synaptic Vesicles, Tissue Distribution, Transcription, Genetic, Sequence Alignment, Glutamic Acid, Membrane Transport Proteins, Amino Acid Transport Systems, Acidic, Vesicular Transport Proteins, Vesicular Glutamate Transport Proteins, Vesicular Glutamate Transport Protein 1, Vesicular Glutamate Transport Protein 2, Rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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