An Ancient Duplication of Exon 5 in the Snap25 Gene Is Required for Complex Neuronal Development/Function
Open accessAbstract
Alternative splicing is an evolutionary innovation to create functionally diverse proteins from a limited number of genes. SNAP-25 plays a central role in neuroexocytosis by bridging synaptic vesicles to the plasma membrane during regulated exocytosis. The SNAP-25 polypeptide is encoded by a single copy gene, but in higher vertebrates a duplication of exon 5 has resulted in two mutually exclusive splice variants, SNAP-25a and SNAP-25b. To address a potential physiological difference between the two SNAP-25 proteins, we generated gene targeted SNAP-25b deficient mouse mutants by replacing the SNAP-25b specific exon with a second SNAP-25a equivalent. Elimination of SNAP-25b expression resulted in developmental defects, spontaneous seizures, and impaired short-term synaptic plasticity. In adult mutants, morphological changes in hippocampus and drastically altered neuropeptide expression were accompanied by severe impairment of spatial learning. We conclude that the ancient exon duplication in the Snap25 gene provides additional SNAP-25-function required for complex neuronal processes in higher eukaryotes.
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Mice carrying genetic substitution of exon 5b with exon 5a exhibit seizures.
“mice carrying genetic substitution of exon 5b with exon 5a also exhibit seizures140.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [140]
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Self-citationHow alternative splicing affects membrane-trafficking dynamics
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A role for alternative splicing in circadian control of exocytosis and glucose homeostasisPreprint
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Replacing SNAP-25b with SNAP-25a expression results in metabolic disease
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Self-citationDifferential contribution of transcriptomic regulatory layers in the definition of neuronal identity
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Modulation of insulin secretion by RBFOX2-mediated alternative splicing
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Epileptogenesis and epileptic maturation in phosphorylation site-specific SNAP-25 mutant mice
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Genetic disorders of neurotransmitter release machinery
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Quantitative mass spectrometry reveals changes in SNAP-25 isoforms in schizophrenia
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SNAP-25a and SNAP-25b differently mediate interactions with Munc18-1 and Gβγ subunits
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Self-citationUpregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control
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Self-citationSimilarity and Diversity of Presynaptic Molecules at Neuromuscular Junctions and Central Synapses
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SNAP-25 Puts SNAREs at Center Stage in Metabolic Disease
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SNAP25 mutation disrupts metabolic homeostasis, steroid hormone production and central neurobehavior
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SNAP‐25 and Gene‐targeted Mouse Mutants
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Retracted: PHOX2B Is Associated with Neuroblastoma Cell Differentiation
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RetractedVesicle trafficking with snares: a perspective for autism
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Adolescent binge ethanol impacts H3K36me3 regulation of synaptic genes
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Self-citationMultiple structural states in an intrinsically disordered protein, SNAP-25, using circular dichroism
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Components controlling vesicle trafficking and regulated exocytosis in pancreatic beta-cells
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Self-citationThe Role of HuD in Alternative Splicing and Alternative Polyadenylation in the Brain
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Kinetic analysis of neuronal SNARE protein interactions
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Synaptopathies auditives et vestibulaires : de la physiologie moléculaire à la thérapie génique
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- Authors
- Johansson, J. U., Ericsson, J., Janson, J., Beraki, S., Stanić, D., Mandic, S. A., Wikström, M. A., Hökfelt, T., Ögren, S. O., Rozell, B., Berggren, P.-O., & Bark, C.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Bark, Christina
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-11-28
- Volume
- 4
- Issue
- 11
- Pages
- e1000278
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2581893
- OpenAlex
- W2024394768
- Cited by
- 83
- References
- 64
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- Gun och Bertil Stohnes Stiftelse
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Novo Nordisk
- Vetenskapsrådet
- Novo Nordisk Fonden
- Marcus och Amalia Wallenbergs minnesfond
- National Institutes of Health
- National Health and Medical Research Council
- 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 › RNA Research and Splicing
- Keywords
- SNAP-25, alternative splicing, gene targeting, neuroexocytosis, synaptic vesicles, spontaneous seizures, short-term plasticity, hippocampus, spatial learning, neuropeptide expression, neuronal development
- MeSH terms
- Doublecortin Domain Proteins, Animals, Exons, Mice, Inbred Strains, Microtubule-Associated Proteins, Neurons, Neuropeptides, Alternative Splicing, Mice, Knockout, Brain-Derived Neurotrophic Factor, Gene Duplication, SNARE Proteins, Synaptosomal-Associated Protein 25, Mice
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