The α1 Subunit EGL-19, the α2/δ Subunit UNC-36, and the β Subunit CCB-1 Underlie Voltage-dependent Calcium Currents in Caenorhabditis elegans Striated Muscle
The α1 Subunit EGL-19, the α2/δ Subunit UNC-36, and the β Subunit CCB-1 Underlie Voltage-dependent Calcium Currents in Caenorhabditis elegans Striated Muscle
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DOI：
10.1074/jbc.m111.256149
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发表时间：
2011-10-21
影响因子：
4.8
通讯作者：
Jospin, Maelle
中科院分区：
文献类型：
--
作者：
Laine, Viviane;Frokjaer-Jensen, Christian;Jospin, Maelle
电压门控钙通道在许多生理过程中发挥关键作用，由一个成孔α 1亚基和三个辅助亚基组成。在脊椎动物中，辅助亚基的作用主要是在异源系统中研究的，主要是因为敲除动物的严重表型。遗传模型秀丽隐杆线虫具有所有主要类型的电压门控钙通道，并且在所有孔形成和辅助亚基中具有强烈的功能丧失突变;因此，它是研究辅助亚基在其天然环境中的作用的有用模型。通过记录通道和辅助亚基突变体的钙电流，我们从分子水平剖析了C.优雅的。我们表明，EGL-19是唯一的α 1亚基，在肌肉细胞中进行钙电流。然后，我们证明了α 2/δ亚基TAG-36调节电压依赖性，激活动力学和钙电流的电导，而另一个α 2/δ亚基TAG-180没有影响。最后，我们表征了两个β亚基CCB-1和CCB-2的突变体。CCB-1是生存所必需的，并且在不存在CCB-1的情况下消除电压依赖性钙电流，而CCB-2不影响电流。总之，这些结果表明，EGL-19、EGL-36和CCB-1是C.秀丽线虫横纹肌。
Voltage-gated calcium channels, which play key roles in many physiological processes, are composed of a pore-forming alpha 1 subunit associated with up to three auxiliary subunits. In vertebrates, the role of auxiliary subunits has mostly been studied in heterologous systems, mainly because of the severe phenotypes of knock-out animals. The genetic model Caenorhabditis elegans has all main types of voltage-gated calcium channels and strong loss-of-function mutations in all pore-forming and auxiliary subunits; it is therefore a useful model to investigate the roles of auxiliary subunits in their native context. By recording calcium currents from channel and auxiliary subunit mutants, we molecularly dissected the voltage-dependent calcium currents in striated muscle of C. elegans. We show that EGL-19 is the only alpha 1 subunit that carries calcium currents in muscle cells. We then demonstrate that the alpha 2/delta subunit UNC-36 modulates the voltage dependence, the activation kinetics, and the conductance of calcium currents, whereas another alpha 2/delta subunit TAG-180 has no effect. Finally, we characterize mutants of the two beta subunits, CCB-1 and CCB-2. CCB-1 is necessary for viability, and voltage-dependent calcium currents are abolished in the absence of CCB-1 whereas CCB-2 does not affect currents. Altogether these results show that EGL-19, UNC-36, and CCB-1 underlie voltage-dependent calcium currents in C. elegans striated muscle.