日本薬理学会年会要旨集
Online ISSN : 2435-4953
第96回日本薬理学会年会
セッションID: 96_4-B-P-302
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一般演題(ポスター)
覚醒維持に関与する新規遺伝子のIn vivo分子解析
*王 乙萌戸根 大輔山田 陸裕上田 泰己
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キーワード: phosphorylation, protein
会議録・要旨集 オープンアクセス

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The molecular basis of mammalian sleep-wake regulation remains largely unexplored. Several studies have identified sleep-regulating kinases that strongly suggest that protein phosphorylation plays a key role in promoting sleep (Tatsuki, 2016; Funato, 2016; Mikhail, 2017), but the regulation of protein phosphorylations involved in the induction and/or maintenance of wakefulness remains unknown. In this study, we identified a novel gene involved in the maintenance of wakefulness. This geneX controls protein phosphorylation in various cellular signaling pathways. AAV-mediated neuronal expression of gene X inhibits the transition from wakefulness to sleep, leading to a marked increase in wake duration in mice.  We also found that this change in wake duration was accompanied by a significant decrease in delta power during NREM sleep. Conversely, inhibition of ProteinX (encoded by geneX) function in neurons resulted in a decrease in wake duration. These results imply that ProteinX is a key regulator of signaling involved in the maintenance of wakefulness. It has been suggested that kinases such as CaMKII are activated during wakefulness and induce sleep, but in contrast, ProteinX might exert its wake-promoting function through interaction with the sleep-promoting kinases.

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