Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.
Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.
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DOI：
10.1038/s41598-017-11319-5
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发表时间：
2017-09-12
影响因子：
4.6
通讯作者：
Iijima T
中科院分区：
文献类型：
--
作者：
Suzuki S;Ayukawa N;Okada C;Tanaka M;Takekoshi S;Iijima Y;Iijima T
选择性剪接是分子多样性的关键，它极大地促进了中枢神经系统（CNS）神经功能的复杂性和特异性。神经成束蛋白（NF）是一种具有多种剪接异构体的多态性细胞表面蛋白。由于神经成束蛋白基因（Nfasc）的选择性剪接受到发育调节，NF亚型在未成熟和成熟的大脑中具有不同的功能。然而，神经元中Nfasc选择性剪接的分子机制尚未被理解。在这里，我们证明，除了发育调控，Nfasc选择性剪接在小鼠大脑中的空间控制。然后，我们在小脑的细胞类型水平上确定了不同的Nfasc剪接模式，Nfas 186在浦肯野细胞中表达，而在颗粒细胞（GC）中不存在。此外，我们发现，高K+诱导的去极化触发的移位，从Nfas 140 Nfas 186在小脑GC的剪接。最后，我们确定了一种神经RNA结合蛋白Rbfox，作为神经NF亚型选择的关键参与者，专门控制外显子26 - 29的剪接。总之，我们的研究结果表明，Nfasc选择性剪接是时空和动态调节小脑神经元。我们的研究结果提供了深刻的洞察机制的神经元细胞粘附蛋白在哺乳动物中枢神经系统的功能多样性。
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.
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影响因子：
8.8
作者：
Weyn-Vanhentenryck SM;Mele A;Yan Q;Sun S;Farny N;Zhang Z;Xue C;Herre M;Silver PA;Zhang MQ;Krainer AR;Darnell RB;Zhang C
通讯作者：
Zhang C
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5.3
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Yamada R;Kuba H
通讯作者：
Kuba H
影响因子：
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Hassel, B;Rathjen, FG;Volkmer, H
通讯作者：
Volkmer, H
影响因子：
4.8
作者：
Kriebel, Martin;Metzger, Jennifer;Volkmer, Hansjuergen
通讯作者：
Volkmer, Hansjuergen
影响因子：
5.3
作者：
Zhang, Ao;Desmazieres, Anne;Brophy, Peter J.
通讯作者：
Brophy, Peter J.