The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation.
The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation.
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DOI：
10.7554/elife.87521
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发表时间：
2023-08-07
期刊：
影响因子：
7.7
通讯作者：
Rihel J
中科院分区：
文献类型：
--
作者：
Barlow IL;Mackay E;Wheater E;Goel A;Lim S;Zimmerman S;Woods I;Prober DA;Rihel J
睡眠是动物行为的一个几乎普遍的特征，但许多分子，遗传和神经元基质，协调睡眠/觉醒过渡尚未发现。通过在斑马鱼幼体中进行病毒插入睡眠筛选，我们发现了一种新的基因dreammist（dmist），它的缺失会导致行为过度活跃和夜间睡眠减少。神经元表达的dmist基因在脊椎动物中是保守的，编码一种结构上类似于Na+，K+-ATP酶调节剂FXYD 1/Phospholemman的小的单程跨膜蛋白。fxyd 1或atp 1a 3a（一种与人类几种遗传性运动障碍相关的Na+，K+-ATP酶α-3亚基）的破坏导致夜间睡眠减少。由于atpa 1a 3a和dmist突变体具有升高的细胞内Na+水平和对夜间睡眠量的非加性效应，因此我们提出，Na+泵功能的Dmist依赖性增强调节神经元兴奋性以维持正常的睡眠行为。
Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+,K+-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na+ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na+ pump function modulates neuronal excitability to maintain normal sleep behaviour.