Moose Devon L, Haase Stephanie J, Aldrich Benjamin T, Lear Bridget C
Department of Biology, University of Iowa, Iowa CityIA, United States.
Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa CityIA, United States.
Front Cell Neurosci. 2017 Jun 6;11:159. doi: 10.3389/fncel.2017.00159. eCollection 2017.
The sodium leak channel NARROW ABDOMEN (NA)/ NALCN is an important component of circadian pacemaker neuronal output. In , rhythmic expression of the NA channel regulator in a subset of adult pacemaker neurons has been proposed to contribute to circadian regulation of channel localization or activity. Here we have restricted expression of NA channel subunits or the regulator to either development or adulthood using the temperature-inducible -GAL80 system. Surprisingly, we find that developmental expression of endogenous channel subunits and is sufficient to promote robust rhythmic behavior in adults. Moreover, we find that channel complex proteins produced during development persist in the head with little decay for at least 5-7 days in adults. In contrast, restricting either endogenous or transgenic gene expression to adult stages produces only limited amounts of the functional channel complex. These data indicate that much of the NA channel complex that functions in adult circadian neurons is normally produced during development, and that the channel complex is very stable in most neurons in the brain. Based on these findings, we propose that circadian regulation of NA channel function in adult pacemaker neurons is mediated primarily by post-translational mechanisms that are independent of
钠泄漏通道窄腹（NA）/NALCN是昼夜节律起搏器神经元输出的重要组成部分。在[具体研究中]，已提出成年起搏器神经元亚群中NA通道调节因子的节律性表达有助于通道定位或活性的昼夜调节。在这里，我们使用温度诱导型GAL80系统将NA通道亚基或调节因子的表达限制在发育阶段或成年阶段。令人惊讶的是，我们发现内源性通道亚基和[调节因子]的发育性表达足以促进成年个体的稳健节律行为。此外，我们发现发育过程中产生的通道复合蛋白在成年个体的头部持续存在，至少5至7天几乎没有衰减。相比之下，将内源性或转基因基因表达限制在成年阶段仅产生有限量的功能性通道复合物。这些数据表明，在成年昼夜节律神经元中起作用的大部分NA通道复合物通常在发育过程中产生，并且该通道复合物在大脑的大多数神经元中非常稳定。基于这些发现，我们提出成年起搏器神经元中NA通道功能的昼夜调节主要由与[具体内容缺失]无关的翻译后机制介导。
