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SV2 Renders Primed Synaptic Vesicles Competent for Ca2+-Induced Exocytosis
Open accessAbstract
Synaptic vesicle protein 2 (SV2), one of the first synaptic vesicle proteins identified, is characterized by multiple transmembrane regions that exhibit homology to sugar transporters, and by a highly glycosylated intravesicular sequence. Deletion of SV2 causes postnatal lethality in mice, primarily because of fulminant epilepsy. At the cellular level, deletion of SV2 impairs neurotransmitter release, but its function is unknown, and even the exact point at which release is affected in SV2-deleted synapses remains unclear. Using electrophysiological approaches, we now examine at what step in exocytosis the deletion of SV2 impairs release. Our data demonstrate that deletion of SV2 produces a decrease in evoked synaptic responses without causing changes in mini frequency, mini amplitude, the readily releasable pool of vesicles, or the apparent Ca 2+sensitivity of vesicle fusion. These findings indicate that a previously unidentified step may couple priming of synaptic vesicles to Ca 2+triggering of fusion, and that SV2 acts in this step to render primed synaptic vesicles fully Ca 2+responsive. To investigate the structural requirements for this function of SV2, we used rescue experiments. We demonstrate that conserved charged residues within the transmembrane regions and the intravesicular glycosylation of SV2 are required for its normal folding and trafficking. In contrast, the conserved putative synaptotagmin-binding sequence of SV2 is fully dispensable. Viewed together, these observations suggest that SV2 functions in a maturation step of primed vesicles that converts the vesicles into a Ca 2+- and synaptotagmin-responsive state.
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“SV2, a marker for mature synaptic vesicles and regulates presynaptic release (70, 71)”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [71]
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Metadata
- Authors
- Chang, W.-P., & Südhof, T. C.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Südhof, Thomas C.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-01-28
- Volume
- 29
- Issue
- 4
- Pages
- 883-897
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2693337
- OpenAlex
- W2039108005
- Cited by
- 176
- References
- 30
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 14 · 2023: 8 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 12 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 10 · 2014: 10 · 2013: 15 · 2012: 19
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- 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
- synaptic vesicle protein 2, SV2, synaptic vesicle priming, neurotransmitter release, vesicle fusion, readily releasable pool, vesicle maturation, epilepsy
- MeSH terms
- Action Potentials, Analysis of Variance, Animals, Animals, Newborn, Calcium, Cells, Cultured, Cerebral Cortex, Egtazic Acid, Electric Stimulation, Exocytosis, Glycosylation, Ionophores, Lysine, Membrane Glycoproteins, Models, Molecular, Mutation, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Picrotoxin, Synaptic Vesicles, Ionomycin, Mice, Knockout, Excitatory Amino Acid Antagonists, 6-Cyano-7-nitroquinoxaline-2,3-dione, GABA Antagonists, Green Fluorescent Proteins, Synaptotagmins, Mice
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