A role for the molecular chaperone protein BiP/GRP78 in Drosophila sleep horneostasis
A role for the molecular chaperone protein BiP/GRP78 in Drosophila sleep horneostasis
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DOI：
10.1093/sleep/30.5.557
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发表时间：
2007-05-01
期刊：
影响因子：
5.6
通讯作者：
Pack, Allan I.
中科院分区：
文献类型：
--
作者：
Naidoo, Nirinjini;Casiano, Vincent;Pack, Allan I.
研究目的：微阵列研究已经确定了许多基因会随着长时间的清醒而发生变化。挑战是确定哪些转录变化转化为蛋白质变化，这些变化对失眠后的恢复至关重要。Bip是内质网(ER)应激的一种蛋白质指标，小鼠和大鼠大脑皮质以及果蝇头部的Bip mRNA因睡眠不足而增加。我们首先试图确定Bip蛋白的表达是否平行于睡眠动态平衡驱动，并随着恢复睡眠而消散。然后，我们试图通过对比BiP过度表达和低表达的模型中的恢复睡眠来确定BIP在睡眠的动态平衡过程中的关键作用。受试者和干预：利用果蝇的UAS-Gal4系统来过度表达野生型Bip和表达显性负型BiP。结果：随着睡眠丧失和恢复睡眠，Bip蛋白增加2.5倍，并伴随着基因的变化。在果蝇中过度表达BIP会导致恢复睡眠的时间增加，同时伴随着未折叠蛋白质反应的延迟。具有显性负突变和功能Bip降低的果蝇表现出相反的效果。结论：我们直接表明，作为ER应激的关键指标，Bip蛋白在决定强制唤醒后的恢复睡眠数量方面发挥了重要作用。因此，我们已经确定了一个调节睡眠内稳态的新窗口。
Study Objectives: Microarray studies have identified numerous genes that change in response to prolonged wakefulness. The challenge is to determine which transcriptional changes translate into protein changes that are critical for recovery following sleep loss. BiP is a protein indicator of endoplasmic reticulum (ER) stress, and BiP mRNA increases in mouse and rat cerebral cortex and in Drosophila heads in response to sleep loss. We first sought to determine whether the expression of BiP protein parallels sleep homeostatic drive and dissipates with recovery sleep. We then sought to establish a key role for BIP in the homeostatic process of sleep by contrasting recovery sleep in models of over- and under-expression of BiP.Subjects and Interventions: Drosophila melanogaster were used to take advantage of the UAS-Gal4 system to both over express wild-type BiP and express a dominant negative form of BiP.Results: BiP protein rises two and a half fold across sleep loss and falls in recovery sleep, in parallel with gene changes. BiP over expression in the flies leads to an increase in recovery sleep in response to sleep loss, in parallel with a delay in the unfolded protein response. Flies with the dominant negative mutation and reduced functional BiP show the opposite effect.Conclusions: We show directly that BiP protein, a key indicator of ER stress is instrumental in determining the amount of recovery sleep following enforced wakefulness. We have thus identified a novel window into regulation of sleep homeostasis.