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首页> 外文期刊>Channels >The juvenile myoclonic epilepsy mutant of the calcium channel β4 subunit displays normal nuclear targeting in nerve and muscle cells
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The juvenile myoclonic epilepsy mutant of the calcium channel β4 subunit displays normal nuclear targeting in nerve and muscle cells

机译：钙通道β4亚基的青少年肌阵挛性癫痫突变体在神经和肌肉细胞中显示正常的核靶向

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摘要

Voltage-gated calcium channels regulate gene expression by controlling calcium entry through the plasma membrane and by direct interactions of channel fragments and auxiliary β subunits with promoters and the epigenetic machinery in the nucleus. Mutations of the calcium channel β_(4) subunit gene (CACNB4 ) cause juvenile myoclonic epilepsy in humans and ataxia and epileptic seizures in mice. Recently a model has been proposed according to which failed nuclear translocation of the truncated β_(4) subunit R482X mutation resulted in altered transcriptional regulation and consequently in neurological disease. Here we examined the nuclear targeting properties of the truncated β_(4b(1–481)) subunit in tsA-201 cells, skeletal myotubes, and in hippocampal neurons. Contrary to expectation, nuclear targeting of β_(4b(1–481)) was not reduced compared with full-length β_(4b) in any one of the three cell systems. These findings oppose an essential role of the β_(4) distal C-terminus in nuclear targeting and challenge the idea that the nuclear function of calcium channel β_(4) subunits is critically involved in the etiology of epilepsy and ataxia in patients and mouse models with mutations in the CACNB4 gene.
机译：电压门控钙通道通过控制钙通过质膜的进入以及通道片段和辅助β亚基与启动子和核中表观遗传机制的直接相互作用来调节基因表达。钙通道β_（4）亚基基因（CACNB4）的突变导致人的青少年肌阵挛性癫痫和共济失调和小鼠的癫痫发作。最近，有人提出了一个模型，根据该模型，截断的β_（4）亚基R482X突变的核移位失败会导致转录调控改变，进而导致神经系统疾病。在这里，我们检查了tsA-201细胞，骨骼肌管和海马神经元中截短的β_（4b（1–481））亚基的核靶向特性。与预期相反，在三个细胞系统中的任何一个中，与全长β_（4b）相比，β_（4b（1–481））的核靶向作用均未降低。这些发现反对了β_（4）远端C末端在核靶向中的重要作用，并挑战了钙通道β_（4）亚基的核功能与患者和小鼠模型中癫痫和共济失调的病因密切相关的观点。 CACNB4基因突变。

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