Cited by 83Cellular transport and secretionNeuroscience and Neuropharmacology ResearchRNA Research and Splicing

An Ancient Duplication of Exon 5 in the Snap25 Gene Is Required for Complex Neuronal Development/Function

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Johansson, Jenny U., Ericsson, Jesper, Janson, Juliette, Beraki, Simret, Stanić, Davor, Mandic, Slavena A., Wikström, Martin A., Hökfelt, Tomas +4 more·2008·PLoS Genetics

Abstract

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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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
Published
2008-11-28
Volume
4
Issue
11
Pages
e1000278
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
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
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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