The SIK3-N783Y mutation is associated with the human natural short sleep trait
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Hongmin Chen
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Ye Xing
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Chunyan Wan
School of Chinese Materia Medica, Nanjing University of Chinese Medicine
Zheng Zhang
Zhu Shi
School of Chinese Materia Medica, Nanjing University of Chinese Medicine
Yutao Liang
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Chunlai Jin
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Yating Chen
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, 94 Weijin Road, Tianjin 300071, China
Xia Zhou
Junyu Xu
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
Louis J. Ptáček
Department of Neurology, University of California San Francisco
Ying-Hui Fu
Department of Neurology, University of California San Francisco
Guangsen Shi
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences