Single-vesicle imaging reveals different transport mechanisms between glutamatergic and GABAergic vesicles
Abstract
Synaptic transmission is mediated by the release of neurotransmitters, which involves exo-endocytotic cycling of synaptic vesicles. To maintain synaptic function, synaptic vesicles are refilled with thousands of neurotransmitter molecules within seconds after endocytosis, using the energy provided by an electrochemical proton gradient. However, it is unclear how transmitter molecules carrying different net charges can be efficiently sequestered while maintaining charge neutrality and osmotic balance. We used single-vesicle imaging to monitor pH and electrical gradients and directly showed different uptake mechanisms for glutamate and γ-aminobutyric acid (GABA) operating in parallel. In contrast to glutamate, GABA was exchanged for protons, with no other ions participating in the transport cycle. Thus, only a few components are needed to guarantee reliable vesicle filling with different neurotransmitters.
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vGAT acts as a GABA/H+ antiporter rather than a GABA/Cl cotransporter and depends on both pH gradient and membrane potential.
“Studies conclude that vGAT acts as a GABA/H+ antiporter rather than a GABA/ClÀ cotransporter and depends on both DpH and DJ.23,24”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [24]
vGAT on synaptic vesicles may have little impact on other transporters on the same vesicle because it depends on both gradients and minimally affects either.
“Therefore, the presence of vGAT on synaptic vesicles may have little impact on the activity of other transporters on the same vesicle, with little effect on their function due to its codependence on DpH and DJ and its minimal effect on either gradient.”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [24]
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- Authors
- Farsi, Z., Preobraschenski, J., van den Bogaart, G., Riedel, D., Jahn, R., & Woehler, A.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- Department of Tumor Immunology, Radboud University Medical Center, 6525GA Nijmegen, Netherlands.
- Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 (DE)
- Corresponding author
- Jahn, Reinhard
- Venue
- Science
- Published
- 2016-02-26
- Volume
- 351
- Issue
- 6276
- Pages
- 981-984
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2269097081
- Cited by
- 96
- References
- 35
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 12 · 2023: 9 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 14 · 2017: 9 · 2016: 4
- FWCI
- 8.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- European Research Council (ERC)
- European Union's Seventh Framework Programme (336479)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- glutamate uptake, GABA uptake, proton gradient, neurotransmitter transport, charge neutrality, osmotic balance, single-vesicle imaging, proton exchange, synaptic transmission
- MeSH terms
- Animals, Biological Transport, Endocytosis, gamma-Aminobutyric Acid, Hydrogen-Ion Concentration, Mice, Transgenic, Synaptic Transmission, Protons, Synaptic Vesicles, Glutamic Acid, Vesicular Inhibitory Amino Acid Transport Proteins, Mice, Molecular Imaging
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