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

Abstract

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.