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Publication : The tight junction protein TJP1 regulates the feeding-modulated hepatic circadian clock.

First Author  Liu Y Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  589
PubMed ID  32001717 Mgi Jnum  J:286080
Mgi Id  MGI:6391993 Doi  10.1038/s41467-020-14470-2
Citation  Liu Y, et al. (2020) The tight junction protein TJP1 regulates the feeding-modulated hepatic circadian clock. Nat Commun 11(1):589
abstractText  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.
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