2. Academic Validation
  3. D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep

D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep

  • Nat Commun. 2019 May 7;10(1):1986. doi: 10.1038/s41467-019-09544-9.
Xihuimin Dai 1,  Enxing Zhou 2,  Wei Yang 1,  Xiaohui Zhang 3,  Wenxia Zhang 1,  Yi Rao 4 5
Affiliations

Affiliations

  • 1 PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
  • 2 College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
  • 4 PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. yrao@pku.edu.cn.
  • 5 Chinese Institute for Brain Research, Beijing, 102206, China. yrao@pku.edu.cn.
PMID: 31064979 DOI: 10.1038/s41467-019-09544-9
Abstract

Natural D-serine (D-Ser) has been detected in Animals more than two decades ago, but little is known about the physiological functions of D-Ser. Here we reveal sleep regulation by endogenous D-Ser. Sleep was decreased in mutants defective in D-Ser synthesis or its receptor the N-methyl-D-aspartic receptor 1 (NMDAR1), but increased in mutants defective in D-Ser degradation. D-Ser but not L-Ser rescued the phenotype of mutants lacking serine racemase (SR), the key Enzyme for D-Ser synthesis. Pharmacological and triple gene knockout experiments indicate that D-Ser functions upstream of NMDAR1. Expression of SR was detected in both the nervous system and the intestines. Strikingly, reintroduction of SR into specific intestinal epithelial cells rescued the sleep phenotype of sr mutants. Our results have established a novel physiological function for endogenous D-Ser and a surprising role for intestinal cells.

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