Analysis of protein dephosphorylation underlying mammalian sleep-wake regulation

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. 95; p. 2-P-126
• Main Authors: 曹, 思鈺, 戸根, 大輔, 山田, 陸裕, 上田, 泰己
• Format: Journal Article
• Language: Japanese; English
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: phosphatase; phosphorylation; protein kinase
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.95.0_2-P-126

Sleep-wake cycle is an organism-level phenomenon that is precisely controlled by multi-layered systems such as molecular, cellular, and circuits in the brain. Among these, recent studies have provided a deeper understanding of the molecular basis of mammalian sleep-wake regulation. Some studies suggest that dynamic changes in the protein phosphorylation in neurons underlie the control of the sleep-wake cycle. However, the core molecular mechanism of this phosphorylation control is still unclear. In this study, we identified a novel sleep-regulating factor in mammal using AAV-based in vivo gene expression system. This geneX is known to be involved in the dephosphorylation process in various signaling pathways. Exogenous expression of the active mutant of the proteinX (encoded by geneX) in neurons resulted in a significant increase in sleep duration. Analysis of the response to external stimuli in these mice suggests that the mice is accompanied by changes in the arousal system. These results imply that the sleep-wake cycle is modulated by a balance between phosphorylation processes that induce acute arousal and dephosphorylation processes involving the geneX that counteract the phosphorylation.