Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.
Satoko SuzukiNoriko AyukawaChisa OkadaMasami TanakaSusumu TakekoshiYoko IijimaTakatoshi IijimaPublished in: Scientific reports (2017)
Alternative splicing is crucial for molecular diversification, which greatly contributes to the complexity and specificity of neural functions in the central nervous system (CNS). Neurofascin (NF) is a polymorphic cell surface protein that has a number of splicing isoforms. As the alternative splicing of the neurofascin gene (Nfasc) is developmentally regulated, NF isoforms have distinct functions in immature and mature brains. However, the molecular mechanisms underlying the alternative splicing of Nfasc in neurons are not yet understood. Here, we demonstrate that, alongside developmental regulation, Nfasc alternative splicing is spatially controlled in the mouse brain. We then identified distinct Nfasc splicing patterns at the cell-type level in the cerebellum, with Nfasc186 being expressed in Purkinje cells and absent from granule cells (GCs). Furthermore, we show that high K+-induced depolarization triggers a shift in splicing from Nfasc140 to Nfasc186 in cerebellar GCs. Finally, we identified a neural RNA-binding protein, Rbfox, as a key player in neural NF isoform selection, specifically controlling splicing at exons 26-29. Together, our results show that Nfasc alternative splicing is spatio-temporally and dynamically regulated in cerebellar neurons. Our findings provide profound insight into the mechanisms underlying the functional diversity of neuronal cell-adhesive proteins in the mammalian CNS.
Keyphrases
- signaling pathway
- induced apoptosis
- binding protein
- cell cycle arrest
- pi k akt
- spinal cord
- lps induced
- cell surface
- oxidative stress
- nuclear factor
- stem cells
- single cell
- inflammatory response
- gene expression
- cell death
- high glucose
- mesenchymal stem cells
- genome wide
- single molecule
- cell proliferation
- cell therapy
- immune response
- autism spectrum disorder
- copy number
- bone marrow