Differential brain expression pattern of Sez6 alternative splicing isoform with deleted transmembrane domain
Differential brain expression pattern of Sez6 alternative splicing isoform with deleted transmembrane domain
复制标题
删除跨膜结构域的 Sez6 选择性剪接亚型的差异脑表达模式
DOI：
10.1016/j.bbrc.2022.10.103
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发表时间：
2022
影响因子：
3.1
通讯作者：
Yuri Kazunari
中科院分区：
文献类型：
--
作者：
Hidaka Chiharu;Mitsui Shinichi;Osako Yoij;Takahashi Kou;Tanaka Kenjiro;Yuri Kazunari
癫痫相关基因 6 (Sez6) 是一种专门位于神经元树突上的跨膜蛋白，负责树突分支和突触形成。选择性剪接产生三种 Sez6mRNA 亚型：显性亚型编码跨膜型蛋白，而两种隐性亚型编码跨膜蛋白和分泌蛋白。在本研究中，为了阐明这些亚型的差异功能，我们在小鼠大脑以及培养的神经元中研究了 Sez6 剪接亚型产生的表达模式。将整个大脑切成1毫米厚的冠状切片，并从这些冠状切片中冲出脑区域。使用 qPCR 技术分析了前额叶皮层、扣带皮层、纹状体、海马和杏仁核中每种 Sez6 亚型的 mRNA 水平，其中 Sez6 表达已在之前报道过，并根据增加的 Sez6 基因表达评估了不同处理条件下培养的原代神经元。我们的结果表明，Sez6 的剪接模式在大脑中受到调节 特定区域的方式。特别是，纹状体显示出隐性亚型的特征剪接模式。此外，惊厥药物刺激的神经元激活增加了隐性亚型，如体外培养的皮质神经元中的显性亚型，在体外培养 5 或 10 天。 总之，Sez6 以及大脑中特异性表达的其他蛋白质的选择性剪接会导致大脑区域特异性表达模式。此外，Sez6的选择性剪接可以通过提高Sez6基因表达的药物来调节。
Seizure-related gene 6 (Sez6) is a transmembrane protein specifically localized on neuronal dendrites and responsible for dendritic branching and synapse formation. Alternative splicing produces three isoforms ofSez6mRNAs: the dominant isoform encodes a transmembrane-type protein, whereas the two recessive isoforms encode transmembrane and secretory proteins. In the present study, to clarify the differential functions of these isoforms, the expression patterns resulting fromSez6splicing isoforms were investigated in the mouse brain as well as in cultured neurons. The whole brains were sliced into coronal sections of 1-mm thickness, and brain areas were punched out from these coronal sections. The mRNA levels of eachSez6isoform in the prefrontal cortex, cingulate cortex, striatum, hippocampus, and amygdala, whereSez6expression has been reported previously, were analyzed using a qPCR technique, and primary neurons cultured under different treatment conditions were assessed in terms of increasedSez6gene expression.Our results show that the splicing patterns ofSez6were modulated in a brain area-specific manner. In particular, the striatum showed a characteristic splicing pattern of recessive isoforms. Moreover, neuronal activation by convulsant drug stimulation increased recessive isoforms like the dominant isoform in cultured cortical neurons at 5 or 10 days in vitro.In conclusion, alternative splicing ofSez6, as well as of other proteins expressed specifically in the brain, results in brain area-specific expression patterns. Furthermore, the alternative splicing ofSez6may be modulated by drugs that elevateSez6gene expression.