Center for Motor Neuron Biology and Disease, Department of Pathology and Cell Biology and Department of Neuroscience, Columbia University Medical Center, New York, New York 10032, USA.
J Neurosci. 2012 May 16;32(20):7058-73. doi: 10.1523/JNEUROSCI.3717-11.2012.
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 Caenorhabditis 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. 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 transsynaptic adhesion. beag and dsmu1 mutants demonstrate an essential role for these previously uncharacterized splicing factors in the regulation of synapse development and function.
前体 mRNA 可变剪接是产生突触蛋白多样性的重要机制，但目前已确定的调控该过程的因素很少。通过对果蝇中突触发育异常的突变体进行筛选，我们发现了 beag 突变体，其突触小泡数量减少，神经递质释放减少。Beag 编码的剪接体蛋白与人类和秀丽隐杆线虫中的剪接因子相似。我们发现，beag 突变体和相互作用基因 dsmu1 的突变体中，特定 Fasciclin II（FasII）剪接异构体的突触水平都发生了变化，FasII 是果蝇神经细胞黏附分子的同源物。我们表明，一种 FasII 剪接异构体的恢复可以挽救 beag 突变体中的突触形态，而其他异构体的表达则不能。我们进一步证明，这种 FasII 异构体在突触发育中具有独特的功能，与跨突触黏附无关。beag 和 dsmu1 突变体表明，这些以前未被描述的剪接因子在调节突触发育和功能方面具有重要作用。
