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首页> 外文期刊>PLoS Genetics >The Dystrophin Complex Controls BK Channel Localization and Muscle Activity in Caenorhabditis elegans
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The Dystrophin Complex Controls BK Channel Localization and Muscle Activity in Caenorhabditis elegans

机译：肌营养不良蛋白复合物控制秀丽隐杆线虫的BK通道定位和肌肉活性。

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Genetic defects in the dystrophin-associated protein complex (DAPC) are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC components from humans to Caenorhabditis elegans suggest a similar molecular function. C. elegans DAPC mutants exhibit a unique locomotory deficit resulting from prolonged muscle excitation and contraction. Here we show that the C. elegans DAPC is essential for proper localization of SLO-1, the large conductance, voltage-, and calcium-dependent potassium (BK) channel, which conducts a major outward rectifying current in muscle under the normal physiological condition. Through analysis of mutants with the same phenotype as the DAPC mutants, we identified the novel islo-1 gene that encodes a protein with two predicted transmembrane domains. We demonstrate that ISLO-1 acts as a novel adapter molecule that links the DAPC to SLO-1 in muscle. We show that a defect in either the DAPC or ISLO-1 disrupts normal SLO-1 localization in muscle. Consistent with observations that SLO-1 requires a high calcium concentration for full activation, we find that SLO-1 is localized near L-type calcium channels in muscle, thereby providing a mechanism coupling calcium influx with the outward rectifying current. Our results indicate that the DAPC modulates muscle excitability by localizing the SLO-1 channel to calcium-rich regions of C. elegans muscle.
机译：肌营养不良蛋白相关蛋白复合物（DAPC）的遗传缺陷可导致多种病理状况，包括肌肉营养不良，心肌病和血管痉挛。从人到秀丽隐杆线虫的保守DAPC组分表明相似的分子功能。秀丽隐杆线虫DAPC突变体表现出独特的运动缺陷，这是由长时间的肌肉兴奋和收缩引起的。在这里，我们显示秀丽隐杆线虫DAPC对于SLO-1的正确定位，大电导，电压和钙依赖性钾（BK）通道至关重要，在正常生理条件下，该通道在肌肉中传导主要的向外整流电流。通过分析与DAPC突变体具有相同表型的突变体，我们鉴定出了新型islo-1基因，该基因编码具有两个预测的跨膜结构域的蛋白质。我们证明，ISLO-1作为一种新型衔接分子，将DAPC链接到肌肉中的SLO-1。我们表明，在DAPC或ISLO-1中的缺陷会破坏正常的SLO-1在肌肉中的定位。与SLO-1需要高浓度的钙才能完全激活的观察结果一致，我们发现SLO-1位于肌肉中L型钙通道附近，从而提供了一种将钙流与向外整流电流耦合的机制。我们的结果表明，DAPC通过将SLO-1通道定位到秀丽隐杆线虫肌肉的钙含量高的区域来调节肌肉的兴奋性。

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