Chen Hongmin, Xing Ye, Wan Chunyan, Zhang Zheng, Shi Zhu, Liang Yutao, Jin Chunlai, Chen Yating, Zhou Xia, Xu Junyu, Ptáček Louis J, Fu Ying-Hui, Shi Guangsen
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528451, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200003, China.
Proc Natl Acad Sci U S A. 2025 May 13;122(19):e2500356122. doi: 10.1073/pnas.2500356122. Epub 2025 May 5.
Sleep is an essential component of our daily life. A mutation in human salt induced kinase 3 (hSIK3), which is critical for regulating sleep duration and depth in rodents, is associated with natural short sleep (NSS), a condition characterized by reduced daily sleep duration in human subjects. This NSS hSIK3-N783Y mutation results in diminished kinase activity in vitro. In a mouse model, the presence of the NSS hSIK3-N783Y mutation leads to a decrease in sleep time and an increase in electroencephalogram delta power. At the phosphoproteomic level, the SIK3-N783Y mutation induces substantial changes predominantly at synaptic sites. Bioinformatic analysis has identified several sleep-related kinase alterations triggered by the SIK3-N783Y mutation, including changes in protein kinase A and mitogen-activated protein kinase. These findings underscore the conserved function of SIK3 as a critical gene in human sleep regulation and provide insights into the kinase regulatory network governing sleep.
睡眠是我们日常生活的重要组成部分。人类盐诱导激酶3（hSIK3）的突变对调节啮齿动物的睡眠时间和深度至关重要，它与自然短睡眠（NSS）有关，NSS是一种人类受试者每日睡眠时间减少的情况。这种NSS hSIK3 - N783Y突变导致体外激酶活性降低。在小鼠模型中，NSS hSIK3 - N783Y突变的存在导致睡眠时间减少和脑电图δ波功率增加。在磷酸化蛋白质组水平上，SIK3 - N783Y突变主要在突触部位引起大量变化。生物信息学分析已经确定了由SIK3 - N783Y突变引发的几种与睡眠相关的激酶改变，包括蛋白激酶A和丝裂原活化蛋白激酶的变化。这些发现强调了SIK3作为人类睡眠调节关键基因的保守功能，并为控制睡眠的激酶调节网络提供了见解。
