Regulation of Fasciclin II and synaptic terminal development by the splicing factor beag.
Regulation of Fasciclin II and synaptic terminal development by the splicing factor beag.
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DOI：
10.1523/jneurosci.3717-11.2012
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发表时间：
2012-05-16
期刊：
影响因子：
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通讯作者：
McCabe BD
中科院分区：
文献类型：
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作者：
Beck ES;Gasque G;Imlach WL;Jiao W;Jiwon Choi B;Wu PS;Kraushar ML;McCabe BD
Pre-mRNA选择性剪接是突触蛋白多样性产生的一个重要机制，但控制这一过程的因素还很少。通过对突触发育异常的果蝇突变体的筛选，我们发现了Beag，一种突触突触较少、神经递质释放减少的突变体。BeAG编码一种剪接体蛋白，类似于人类和线虫中的剪接因子。我们发现，BAAG突变体和相互作用基因dsmu1的突触水平都改变了果蝇神经细胞黏附分子(NCAM)的同源基因Fasciclin II(FasII)的特定剪接异构体的突触水平。我们发现，恢复FasII的一个剪接异构体可以挽救beag突变体的突触形态，而表达其他异构体则不能。我们进一步证明，这个FasII亚型在突触发育中具有独特的功能，而不依赖于跨突触的黏附。Beag和dsmu1突变体显示了这些以前未知的剪接因子在调节突触发育和功能中的重要作用。
Pre-mRNA alternative splicing is an important mechanism for the generation of synaptic protein diversity, but few factors governing this process have been identified. From a screen for Drosophila mutants with aberrant synaptic development, we identified beag, a mutant with fewer synaptic boutons and decreased neurotransmitter release. Beag encodes a spliceosomal protein similar to splicing factors in humans and C. elegans. We find that both beag mutants and mutants of an interacting gene dsmu1 have changes in the synaptic levels of specific splice isoforms of Fasciclin II (FasII), the Drosophila ortholog of Neural Cell Adhesion Molecule (NCAM). We show that restoration of one splice isoform of FasII can rescue synaptic morphology in beag mutants while expression of other isoforms cannot. We further demonstrate that this FasII isoform has unique functions in synaptic development independent of trans-synaptic adhesion. beag and dsmu1 mutants demonstrate an essential role for these previously uncharacterized splicing factors in the regulation of synapse development and function.