CK2 Regulation of Fragile X in Circadian Clocks

CK2 对昼夜节律中脆弱 X 的调节

• 批准号: 7157267
• 负责人: Elaine M Smith
• 金额: $ 4.88万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157267
• 关键词: Drosophilidae; RNA binding protein; arthropod genetics; behavioral /social science research tag; behavioral genetics; casein kinase; circadian rhythms; developmental genetics; enzyme activity; enzyme mechanism; fragile X syndromes; gene expression; gene mutation; genetic regulation; immunoprecipitation; mental retardation; molecular genetics; neurochemistry; phosphorylation; postdoctoral investigator; protein protein interaction; psychomotor function

DESCRIPTION (provided by applicant): Fragile X mental retardation is the most common form of inherited mental disorders, and occurs due to the loss of a single gene, FMR. In Drosophila, it was revealed that dFMR plays a role in modulating circadian locomotor behavior. dFMR is phosphorylated by CK2, and loss of this kinase also impairs function of the clock. While aspects of the core transcriptional feedback loop that drives the clock have been well defined, little is known about the way in which the clock communicates timing information. We hypothesize that dfmr and CK2 interact in vivo and that dfmr function in Drosophila pacemaker neurons influences output of the circadian clock. To test these ideas in vivo behavioral, genetic, and molecular investigations of the interaction between dFMR and CK2 will be employed. Results of this study may uncover an example of dfmr regulation in the circadian rhythm pathway and provide novel means of adjusting circadian outputs to modulate sleep and other daily rhythms. Moreover, analysis of dfmr will bring about increased understanding of the function, and consequence of loss, of this disease gene, potentially leading to unique interventions in Fragile X mental retardation.

描述（由申请人提供）：脆性 X 型精神发育迟滞是遗传性精神障碍的最常见形式，是由于单个基因 FMR 的缺失而发生的。在果蝇中，研究表明 dFMR 在调节昼夜运动行为中发挥作用。 dFMR 被 CK2 磷酸化，这种激酶的丢失也会损害时钟功能。虽然驱动时钟的核心转录反馈环路的各个方面已经得到了很好的定义，但人们对时钟传递定时信息的方式知之甚少。我们假设 dfmr 和 CK2 在体内相互作用，并且果蝇起搏神经元中的 dfmr 功能影响生物钟的输出。为了测试这些想法，将采用 dFMR 和 CK2 之间相互作用的体内行为、遗传和分子研究。这项研究的结果可能会揭示昼夜节律通路中 dfmr 调节的一个例子，并提供调整昼夜节律输出以调节睡眠和其他日常节律的新方法。此外，对 dfmr 的分析将加深对该疾病基因的功能和损失后果的了解，从而有可能对脆性 X 型智力迟钝进行独特的干预。