Investigation of dephosphorylation of synaptic phosphoproteins engaged in mammalian sleep-wake regulation

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. 96; p. 2-B-P-118
• Main Authors: Siyu, Cao, Tone, Daisuke, Yamada, Rikuhiro, Sumiyama, Kenta, Ueda, Hiroki
• Format: Journal Article
• Language: Japanese; English
• Published: Japanese Pharmacological Society 2022
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.96.0_2-B-P-118

Sleep-wake cycle is an organism-level phenomenon that is precisely controlled by multi-layered systems such as circuits, cellular and molecular levels in a brain. Recent studies have provided a deeper understanding of the molecular basis of mammalian sleep-wake regulation and some studies suggested dynamic changes in neuronal protein phosphorylation under the control of the sleep-wake cycle. However, the core molecular mechanism of the dynamic changes in phospho-proteins and whether it could drive the transition between sleep and wake is still unclear. In this study, we identified a gene known to be involved in the dephosphorylation process in various signaling pathways in mammals as a novel sleep-regulating factor. Exogenous expression of the active form of GeneX in excitatory postsynapses resulted in a significant increase in sleep duration. Besides, knockout of one of geneX regulators which works as the scaffold protein of the proteinX in excitatory postsynapses resulted in a significant decrease in sleep duration. These results suggest that the sleep-wake cycle is modulated by dephosphorylation processes involving proteinX in the excitatory postsynapses.