ppGpp is present in,and functions to regulate sleep of,Drosophila  

作　　者：Xihuimin Dai Wei Yang Xiaohui Zhang Enxing Zhou Renbo Mao Ying Liu Tao Wang Wenxia Zhang Xinxiang Zhang Yi Rao 

机构地区：[1]Peking-Tsinghua Center for Life Sciences,PKU-IDG/McGovern Institute for Brain Research,Peking University School of Life Sciences,and Chinese Institute for Brain Research,Beijing,China [2]Howard Hughes Medical Institute,Department of Biology,Brandeis University,Waltham,United States [3]State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing,China [4]College of Chemistry and Molecular Engineering,Peking University,Beijing,China [5]Capital Medical University,Beijing,China

出　　处：《hLife》2023年第2期98-114,共17页健康科学（英文）

基　　金：National Natural Science Foundation of China (32061143017 to Y.R.);the Research Unit of Medical Neurobi-ology,Chinese Academy of Medical Sciences (No.2019RU003)for grant support.

摘　　要：Sleep is essential for animals,and receives inputs from circadian,homeostasis,and environment,yet the mechanisms of sleep regulation remain elusive.Discovery of molecules in living systems and demonstration of their functional roles are pivotal in furthering our understanding of the molecular basis of biology.Here,we report that guanosine-50-diphos-phate,30-diphosphate(ppGpp)is present in Drosophila,and plays an important role in regulation of sleep and starvation-induced sleep loss(SISL).ppGpp is detected in germ-free Drosophila and hydrolyzed by an enzyme encoded by the mesh1 gene in Drosophila.Nighttime sleep and SISL were defected in mesh1 mutant flies,and rescued by expression of wildtype Mesh1,but not the enzymatically defective mutant Mesh1E66A.Ectopic expression of RelA,the Escherichia coli synthetase for ppGpp,phenocopied mesh1 knockout mutants,whereas overexpression of Mesh1 resulted in the opposite phenotypes,supporting that ppGpp is both necessary and sufficient in sleep regulation.A chemo connectomic screen followed by genetic intersection experiments implicates the Dilp2 neurons in the pars intercerebralis(PI)brain region as the site of ppGpp function.Our results have thus validated the presence of ppGpp in Drosophila and revealed a physiological role of ppGpp in sleep regulation for the first time.

关 键 词：SLEEP Mesh1 DROSOPHILA PPGPP STARVATION 

分 类 号：Q96[生物学—昆虫学]