Yeh Edward, Ng Sharon, Zhang Mi, Bouhours Magali, Wang Ying, Wang Min, Hung Wesley, Aoyagi Kyota, Melnik-Martinez Katya, Li Michelle, Liu Fang, Schafer William R, Zhen Mei
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
PLoS Biol. 2008 Mar 11;6(3):e55. doi: 10.1371/journal.pbio.0060055.
Voltage-gated cation channels regulate neuronal excitability through selective ion flux. NALCN, a member of a protein family that is structurally related to the alpha1 subunits of voltage-gated sodium/calcium channels, was recently shown to regulate the resting membrane potentials by mediating sodium leak and the firing of mouse neurons. We identified a role for the Caenorhabditis elegans NALCN homologues NCA-1 and NCA-2 in the propagation of neuronal activity from cell bodies to synapses. Loss of NCA activities leads to reduced synaptic transmission at neuromuscular junctions and frequent halting in locomotion. In vivo calcium imaging experiments further indicate that while calcium influx in the cell bodies of egg-laying motorneurons is unaffected by altered NCA activity, synaptic calcium transients are significantly reduced in nca loss-of-function mutants and increased in nca gain-of-function mutants. NCA-1 localizes along axons and is enriched at nonsynaptic regions. Its localization and function depend on UNC-79, and UNC-80, a novel conserved protein that is also enriched at nonsynaptic regions. We propose that NCA-1 and UNC-80 regulate neuronal activity at least in part by transmitting depolarization signals to synapses in C. elegans neurons.
电压门控阳离子通道通过选择性离子通量调节神经元兴奋性。NALCN是一个蛋白质家族的成员，在结构上与电压门控钠/钙通道的α1亚基相关，最近研究表明它通过介导钠泄漏和调节小鼠神经元的放电来调控静息膜电位。我们确定了秀丽隐杆线虫NALCN同源物NCA-1和NCA-2在神经元活动从细胞体向突触传播中的作用。NCA活性丧失会导致神经肌肉接头处的突触传递减少以及运动频繁停止。体内钙成像实验进一步表明，虽然产卵运动神经元细胞体中的钙内流不受NCA活性改变的影响，但在nca功能丧失突变体中突触钙瞬变显著减少，而在nca功能获得突变体中则增加。NCA-1定位于轴突并在非突触区域富集。其定位和功能依赖于UNC-79以及UNC-80，UNC-80是一种同样在非突触区域富集的新型保守蛋白。我们提出，NCA-1和UNC-80至少部分通过将去极化信号传递到秀丽隐杆线虫神经元的突触来调节神经元活动。
