睡眠促进因子SLEEPLESS的鉴定。
Identification of SLEEPLESS, a sleep-promoting factor.
作者信息
Koh Kyunghee, Joiner William J, Wu Mark N, Yue Zhifeng, Smith Corinne J, Sehgal Amita
机构信息
Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Science. 2008 Jul 18;321(5887):372-6. doi: 10.1126/science.1155942.
Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.
睡眠是从果蝇到人类都保守存在的一个基本过程。睡眠严格的稳态控制突出了其重要性。通过正向遗传学筛选，我们在果蝇中鉴定出一个睡眠所需的基因——无眠基因。无眠基因编码一种在大脑中富集的、糖基磷脂酰肌醇锚定蛋白。无眠蛋白的缺失导致睡眠极度减少（超过80%）；无眠蛋白适度减少对基础睡眠影响极小，但显著减少睡眠剥夺后的恢复睡眠量。遗传和分子分析表明，颤动（一种损害依赖于Shaker的钾电流的突变）是无眠基因的一个等位基因。与这一发现一致，在无眠突变体中Shaker蛋白水平降低。我们提出，无眠蛋白是一种将睡眠驱动力与降低的膜兴奋性联系起来的信号分子。
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