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

Nat Commun. 2020 Jan 30;11(1):589. doi: 10.1038/s41467-020-14470-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Circadian Clocks / physiology*
  • Dogs
  • Feeding Behavior*
  • HEK293 Cells
  • Hepatocytes / metabolism
  • Humans
  • Insulin Resistance
  • Liver / physiology*
  • Madin Darby Canine Kidney Cells
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Mutation / genetics
  • Period Circadian Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Zonula Occludens-1 Protein / metabolism*


  • Per1 protein, mouse
  • Period Circadian Proteins
  • RNA, Messenger
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein
  • TOR Serine-Threonine Kinases