The tight junction protein TJP1 regulates the feeding-modulated hepatic circadian clock
The tight junction protein TJP1 regulates the feeding-modulated hepatic circadian clock
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DOI：
10.1038/s41467-020-14470-2
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发表时间：
2020-01-30
影响因子：
16.6
通讯作者：
Wang, Yiguo
中科院分区：
文献类型：
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作者：
Liu, Yi;Zhang, Yuanyuan;Wang, Yiguo
视交叉上核和外周组织中的昼夜节律钟协调哺乳动物对环境线索的行为和生理活动。在肝脏中，昼夜节律钟也受到进食的调节。然而，涉及的分子机制尚不清楚。在这里，我们表明TJP 1（紧密连接蛋白1）作为mTOR（雷帕霉素的机制靶点）的介导剂调节肝脏昼夜节律钟。TJP1与PER1（period circadian regulator 1）相互作用并阻止其核转位。在进食期间，mTOR磷酸化TJP 1并减弱其与PER 1的关联，从而增强PER 1的核穿梭以抑制昼夜节律振荡。因此，我们的研究结果提供了一个以前未表征的机制如何喂养调节肝脏昼夜节律钟的见解。生物钟调节生理和新陈代谢的节奏，以响应环境线索，如食物摄入。在这里，作者表明，紧密连接蛋白1（TJP 1）与第1阶段相互作用，并以mTOR依赖性方式调节其核转位。
Circadian clocks in the suprachiasmatic nucleus and peripheral tissues orchestrate behavioral and physiological activities of mammals in response to environmental cues. In the liver, the circadian clock is also modulated by feeding. However, the molecular mechanisms involved are unclear. Here, we show that TJP1 (tight junction protein 1) functions as a mediator of mTOR (mechanistic target of rapamycin) to modulate the hepatic circadian clock. TJP1 interacts with PER1 (period circadian regulator 1) and prevents its nuclear translocation. During feeding, mTOR phosphorylates TJP1 and attenuates its association with PER1, thereby enhancing nuclear shuttling of PER1 to dampen circadian oscillation. Therefore, our results provide a previously uncharacterized mechanistic insight into how feeding modulates the hepatic circadian clock. The circadian clock regulates rhythms of physiology and metabolism in response to environmental cues such as food intake. Here, the authors show that tight junction protein 1 (TJP1) interacts with period 1 and modulates its nuclear translocation in a mTOR-dependent manner.