Chen Xiupeng, Li Jie, Gao Zhongbao, Yang Yang, Kuang Wenqing, Dong Yue, Chua Gek Huey, Huang Xiahe, Jiang Binhua, Tian He, Wang Yingchun, Huang Xun, Li Yan, Lam Sin Man, Shui Guanghou
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Natl Sci Rev. 2022 Jul 27;9(12):nwac148. doi: 10.1093/nsr/nwac148. eCollection 2022 Dec.
While endogenous lipids are known to exhibit rhythmic oscillations, less is known about how specific lipids modulate circadian behavior. Through a series of loss-of-function and gain-of-function experiments on ceramide phosphoethanolamine (CPE) synthase of , we demonstrated that pan-glial-specific deficiency in membrane CPE, the structural analog of mammalian sphingomyelin (SM), leads to arrhythmic locomotor behavior and shortens lifespan, while the reverse is true for increasing CPE. Comparative proteomics uncovered dysregulated synaptic glutamate utilization and transport in CPE-deficient flies. An extensive genetic screen was conducted to verify the role of differentially expressed proteins in circadian regulation. Arrhythmic locomotion under mutant background was rescued only by restoring endogenous CPE or SM through expressing their respective synthases. Our results underscore the essential role of CPE in maintaining synaptic glutamate homeostasis and modulating circadian behavior in . The findings suggest that region-specific elevations of functional membrane lipids can benefit circadian regulation.
虽然已知内源性脂质会呈现节律性振荡，但对于特定脂质如何调节昼夜节律行为却知之甚少。通过对[具体物种]的神经酰胺磷酸乙醇胺（CPE）合酶进行一系列功能丧失和功能获得实验，我们证明，膜CPE（哺乳动物鞘磷脂（SM）的结构类似物）的全神经胶质特异性缺陷会导致运动行为节律紊乱并缩短寿命，而增加CPE则会产生相反的效果。比较蛋白质组学揭示了CPE缺陷果蝇中突触谷氨酸利用和转运的失调。进行了广泛的遗传筛选，以验证差异表达蛋白在昼夜节律调节中的作用。只有通过表达各自的合酶来恢复内源性CPE或SM，才能挽救[突变背景下的]节律性运动。我们的结果强调了CPE在维持[具体物种]突触谷氨酸稳态和调节昼夜节律行为中的重要作用。这些发现表明，功能性膜脂质的区域特异性升高可能有益于昼夜节律调节。
