An ancient duplication of exon 5 in the Snap25 gene is required for complex neuronal development/function

Jenny U. Johansson, Jesper Ericsson, Juliette Janson, Simret Beraki, Davor Stanić, Slavena A. Mandic, Martin A. Wikström, Tomas Hökfelt, Sven Ove Ögren, Björn Rozell, Per Olof Berggren, Christina Bark

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Article numbere1000278
JournalPLoS genetics
Volume4
Issue number11
DOIs
StatePublished - Nov 2008

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    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. (2008). An ancient duplication of exon 5 in the Snap25 gene is required for complex neuronal development/function. PLoS genetics, 4(11), [e1000278]. https://doi.org/10.1371/journal.pgen.1000278