An ancient duplication of exon 5 in the Snap25 gene is required for complex neuronal development/function.
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.
Johansson
Jenny U
JU
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
Ericsson
Jesper
J
Janson
Juliette
J
Beraki
Simret
S
Stanić
Davor
D
Mandic
Slavena A
SA
Wikström
Martin A
MA
Hökfelt
Tomas
T
Ogren
Sven Ove
SO
Rozell
Björn
B
Berggren
Per-Olof
PO
Bark
Christina
C
D017398:Alternative Splicing; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D005091:Exons / Q000235:genetics*; D020440:Gene Duplication; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D050600:SNARE Proteins; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25