HongminChena,1,YeXinga,b,c,1,ChunyanWand,1, ZhengZhanga,e, ZhuShid,YutaoLianga,c,ChunlaiJina,b,c,YatingChena,XiaZhoua,JunyuXua,b,c, LouisJ. Ptáčekf,g,h, Ying-Hui Fuf,g,h,2, and Guangsen Shia,b,c,d,e,2

• 成果类型: Article
• 署名作者: Chen, Hongmin; Xing, Ye; Wand, Chunyan; Zhang, Zheng; Shid, Zhu; Liang, Yutao; Jin, Chunlai; Chen, Yating; Zhou, Xia; Xu, Junyu; Ptacek, Louis J.; Fu, Ying-Hui; Shi, Guangsen
• 署名单位: Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Nanjing University of Chinese Medicine; Guangzhou University of Chinese Medicine; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10350
• DOI: 10.1073/pnas.2500356122
• 发表日期: 2025-05-13
• 关键词: sleep; mutations; genetics; PATHWAY; kinase; ampk

摘要

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.