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

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 re...

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Autores principales: Dai, Xihuimin, Zhou, Enxing, Yang, Wei, Zhang, Xiaohui, Zhang, Wenxia, Rao, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504911/
https://www.ncbi.nlm.nih.gov/pubmed/31064979
http://dx.doi.org/10.1038/s41467-019-09544-9
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author Dai, Xihuimin
Zhou, Enxing
Yang, Wei
Zhang, Xiaohui
Zhang, Wenxia
Rao, Yi
author_facet Dai, Xihuimin
Zhou, Enxing
Yang, Wei
Zhang, Xiaohui
Zhang, Wenxia
Rao, Yi
author_sort Dai, Xihuimin
collection PubMed
description 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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spelling pubmed-65049112019-05-09 D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep Dai, Xihuimin Zhou, Enxing Yang, Wei Zhang, Xiaohui Zhang, Wenxia Rao, Yi Nat Commun Article 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. Nature Publishing Group UK 2019-05-07 /pmc/articles/PMC6504911/ /pubmed/31064979 http://dx.doi.org/10.1038/s41467-019-09544-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dai, Xihuimin
Zhou, Enxing
Yang, Wei
Zhang, Xiaohui
Zhang, Wenxia
Rao, Yi
D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep
title D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep
title_full D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep
title_fullStr D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep
title_full_unstemmed D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep
title_short D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep
title_sort d-serine made by serine racemase in drosophila intestine plays a physiological role in sleep
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504911/
https://www.ncbi.nlm.nih.gov/pubmed/31064979
http://dx.doi.org/10.1038/s41467-019-09544-9
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