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Differential Control of the Releasable Vesicle Pools by SNAP-25 Splice Variants and SNAP-23
Open accessAbstract
The SNARE complex, consisting of synaptobrevin, syntaxin, and SNAP-25, is essential for calcium-triggered exocytosis in neurosecretory cells. Little is known, however, about how developmentally regulated isoforms and other cognate SNARE components regulate vesicular fusion. To address this question, we examined neuroexocytosis from chromaffin cells of Snap25 null mice rescued by the two splice variants SNAP-25a and SNAP-25b and the ubiquitously expressed homolog SNAP-23. In the absence of SNAP-25, vesicle docking persisted, but primed vesicle pools were empty and fast calcium-triggered release abolished. Single vesicular fusion events showed normal characteristics, except for a shorter duration of the fusion pore. Overexpression of SNAP-25a, SNAP-25b, and SNAP-23 resulted in three distinct phenotypes; SNAP-25b induced larger primed vesicle pools than SNAP-25a, whereas SNAP-23 did not support a standing pool of primed vesicles. We conclude that three alternative SNARE components support exocytosis, but they differ in their ability to stabilize vesicles in the primed state.
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“that show differences in the kinetics of synaptic vesicle release138,139.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [138]
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“the gene for the SNARE protein SNAP25 uses a pair of mutually exclusive exons (5a and 5b) to produce two alternative isoforms”
From The neurogenetics of alternative splicing (2016) · cites this paper as [138]
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Metadata
- Authors
- Sørensen, J. B., Nagy, G., Varoqueaux, F., Nehring, R. B., Brose, N., Wilson, M. C., & Neher, E.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- Max Planck Institute of Experimental Medicine (DE)
- University of New Mexico (US)
- Corresponding author
- Sørensen, Jakob B.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 114
- Issue
- 1
- Pages
- 75-86
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2137163623
- Cited by
- 364
- References
- 41
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 12 · 2020: 11 · 2019: 11 · 2018: 13 · 2017: 12 · 2016: 14 · 2015: 17 · 2014: 13 · 2013: 13 · 2012: 11
- FWCI
- 9.50
- 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, 3669 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
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- International Max Planck Research School for Environmental, Cellular and Molecular Microbiology
- Deutsche Forschungsgemeinschaft (SFB523)
- National Institutes of Health
- National Institute of Mental Health (MH 4-8989, R01MH048989)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- SNAP-25, SNAP23, SNARE complex, chromaffin cells, neuroexocytosis, calcium-triggered exocytosis, vesicle docking, vesicle fusion, fusion pore, splice variants
- MeSH terms
- Animals, Calcium, Carrier Proteins, Exocytosis, Fetus, Membrane Fusion, Membrane Proteins, Nerve Tissue Proteins, Neurosecretion, Neurosecretory Systems, Phenotype, Alternative Splicing, Mice, Knockout, Chromaffin Cells, Calcium Signaling, Secretory Vesicles, Qb-SNARE Proteins, Qc-SNARE Proteins, Synaptosomal-Associated Protein 25, Mice
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