论文标题：D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep

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作者：Xihuimin Dai, Enxing Zhou, Wei Yang, Xiaohui Zhang, Wenxia Zhang, Yi Rao

发表时间：2019/05/07

数字识别码： 10.1038/s41467-019-09544-9

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《自然-通讯》本周在线发表的一篇论文D-Serine made by serine racemase in Drosophila intestine plays a physiological role in sleep指出，一种肠道合成的氨基酸对调节果蝇（Drosophila）睡眠具有重要作用。这种氨基酸名为D-丝氨酸，存在于在果蝇和哺乳动物中，研究结果有望带来睡眠调节的全新认识。

图1：shmt突变体的睡眠表型。图源：Dai等

D-丝氨酸曾被认为只存在于细菌中，但app家近来发现这种氨基酸也天然存在于人体内。不过，此前对D-丝氨酸生理功能的认识尚属空白，只有一些研究显示D-丝氨酸对人类大脑具有潜在作用。

北京大学的饶毅和同事对携带不同遗传变异的果蝇进行了筛选，从中发现了一个睡眠紊乱较为显著的变异体。作者研究了这支果蝇突变系中受到破坏的基因，发现参与D-丝氨酸合成与降解的基因受到了影响。如果缺少合成D-丝氨酸的丝氨酸消旋酶（SR），睡眠也会减少。作者还发现，虽然SR在神经系统和肠道中都有表达，但只有肠道中的SR活性对睡眠调节具有重要的功能意义。

图2：shmt, sr, daao 和nmdar1的表达模式。图源：Dai等

还需要开展进一步研究确定其它身体器官是否会表达SR，以及肠道合成的氨基酸如何能对传统上认为受中枢神经系统控制的睡眠过程产生影响。

摘要：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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