The role of neural translin in metabolic control of sleep

神经转运蛋白在睡眠代谢控制中的作用

• 批准号: 8719396
• 负责人: Alex C Keene
• 金额: $ 29.71万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719396
• 关键词: Acetylcholine; Acute; Adult; Animals; Behavior; Behavioral; Cells; Choline O-Acetyltransferase; DNA-Binding Proteins; Desire for food; Development; Diabetes Mellitus; Disease; Drosophila genus; Drosophila melanogaster; Failure; Food; Genes; Genetic; Genetic Processes; Glucose; Head; Health; Heart Atrium; Homeostasis; Human; Image; Insulin; Insulin Receptor; Investigation; Label; Link; Mammals; Measures; Messenger RNA; Metabolic; Metabolic Control; Metabolic Diseases; Metabolic syndrome; Metabolism; Mutation; Nervous system structure; Neurons; Neuropeptides; Nutrient; Nutritional; Obesity; Pathology; Peptides; Phenocopy; Physiology; Population; Prevalence; Proxy; RNA Interference; Rattus; Receptor Activation; Regulation; Role; Sleep; Sleep Disorders; Starvation; System; Testing; Transcriptional Regulation; Transgenic Organisms; Work; base; feeding; fly; insulin signaling; knock-down; mutant; neuroregulation; pancreatic secretory trypsin inhibitor I; pressure; public health relevance; receptor function; relating to nervous system; research study; response; sensor; sleep regulation; tool

Proposal Summary Neural regulation of sleep, appetite and energy homeostasis is critical to an animal's survival and under stringent evolutionary pressure. Dysregulation of sleep is strongly linked to obesity, diabetes, and metabolic disease. Despite the prevalence of disorders associated with metabolism and sleep, the neural and genetic processes that regulate interactions between these two systems is unclear. This proposal will investigate how genes and neurons modulate sleep in response to changes in metabolism. Flies, like mammals, potently modulate sleep in accordance with their nutritional needs. Specifically, flies and mammals suppress sleep in response to starvation, presumably to initiate food-seeking behavior. Powerful genetics in the fruit fly allow for precise characterization of genes regulating behavioral and metabolic processes. I recently carried out a neuron-specific RNA interference screen of over 1100 genes revealed numerous targets that are required for metabolic regulation of sleep. In particular, this screen isolated translin (trsn), an mRNA/DNA binding protein that is highly conserved from flies to humans. Neuron specific knock-down or mutations in the trsn locus results in flies that fail suppress sleep during starvation, but have normal energy stores trsn is highly conserved across phyla and has a putative role in mammalian metabolic function. This proposal seeks to characterize the cellular and neuroanatomical function of trsn to determine how sleep and metabolic state are integrated. This work will define a critical link between metabolism and sleep regulation, providing new avenues for investigating sleep-feeding interactions that potently impact human health. Functional investigation of genes regulating sleep-metabolism interactions will provide the groundwork for understanding metabolic regulation of behavior and further our understanding of obesity, sleep disorders and diabetes.

提案摘要 睡眠、食欲和能量稳态的神经调节对动物的生存至关重要，并且在严格的环境下， 进化的压力睡眠失调与肥胖、糖尿病和代谢疾病密切相关。 尽管与新陈代谢和睡眠有关的疾病普遍存在，但神经和遗传过程 调节这两个系统之间相互作用的机制尚不清楚。这项提案将研究基因和 神经元调节睡眠以响应新陈代谢的变化。苍蝇和哺乳动物一样， 根据他们的营养需求。具体来说，苍蝇和哺乳动物抑制睡眠， 饥饿，可能是为了启动觅食行为。果蝇强大的遗传学允许精确的 表征调控行为和代谢过程的基因。我最近做了一个神经元特异性的 超过1100个基因的RNA干扰筛选揭示了代谢所需的许多靶点。 睡眠的调节。特别地，该筛选分离了translin（trsn），其是一种mRNA/DNA结合蛋白， 从苍蝇到人类都保存了下来。神经元特异性敲除或trsn基因座突变导致果蝇不能 在饥饿期间抑制睡眠，但具有正常能量储存TRSN在门中高度保守， 在哺乳动物代谢功能中的推定作用。该提案寻求表征蜂窝和 TRSN的神经解剖学功能，以确定睡眠和代谢状态是如何整合的。这项工作将 定义代谢和睡眠调节之间的关键联系，为研究提供新的途径 睡眠-进食的相互作用，这可能会对人类健康产生重大影响。基因调控的功能研究 睡眠-代谢的相互作用将为理解行为的代谢调节提供基础 进一步加深我们对肥胖、睡眠障碍和糖尿病的理解。