Endogenous ceramide phosphoethanolamine modulates circadian rhythm via neural-glial coupling in Drosophila  

作　　者：Xiupeng Chen Jie Li Zhongbao Gao Yang Yang Wenqing Kuang Yue Dong Gek Huey Chua Xiahe Huang Binhua Jiang He Tian Yingchun Wang Xun Huang Yan Li Sin Man Lam Guanghou Shui 

机构地区：[1]State Key Laboratory of Molecular Developmental Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]State Key Laboratory of Brain and Cognitive Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [4]Lipid ALL Technologies Company Limited,Changzhou 213022,China

出　　处：《National Science Review》2022年第12期98-117,共20页国家科学评论（英文版）

基　　金：supported bythe National Natural Science Foundationof China(92057202);the National KeyR&D Program of China(2018YFA0506900,2018YFA0800901 and 2019YFA0802402).

摘　　要：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 cer amide phosphoethanolamine(CPE)synthase of Drosophila,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 cpes1 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 Drosophila.The findings suggest that region-specific elevations of functional membrane lipids can benefit circadian regulation.

关 键 词：ceramide phosphoethanolamine SPHINGOMYELIN CIRCADIAN LONGEVITY glutamate homeostasis 

分 类 号：Q41[生物学—生理学]