| First Author | Pilorz V | Year | 2014 |
| Journal | Curr Biol | Volume | 24 |
| Issue | 7 | Pages | 766-73 |
| PubMed ID | 24656826 | Mgi Jnum | J:252802 |
| Mgi Id | MGI:5926599 | Doi | 10.1016/j.cub.2014.02.027 |
| Citation | Pilorz V, et al. (2014) A novel mechanism controlling resetting speed of the circadian clock to environmental stimuli. Curr Biol 24(7):766-73 |
| abstractText | Many aspects of mammalian physiology are driven through the coordinated action of internal circadian clocks. Clock speed (period) and phase (temporal alignment) are fundamental to an organism's ability to synchronize with its environment. In humans, lifestyles that disturb these clocks, such as shift work, increase the incidence of diseases such as cancer and diabetes. Casein kinases 1delta and epsilon are closely related clock components implicated in period determination. However, CK1delta is so dominant in this regard that it remains unclear what function CK1epsilon normally serves. Here, we reveal that CK1epsilon dictates how rapidly the clock is reset by environmental stimuli. Genetic disruption of CK1epsilon in mice enhances phase resetting of behavioral rhythms to acute light pulses and shifts in light cycle. This impact of CK1epsilon targeting is recapitulated in isolated brain suprachiasmatic nucleus and peripheral (lung) clocks during NMDA- or temperature-induced phase shift in association with altered PERIOD (PER) protein dynamics. Importantly, accelerated re-entrainment of the circadian system in vivo and in vitro can be achieved in wild-type animals through pharmacological inhibition of CK1epsilon. These studies therefore reveal a role for CK1epsilon in stabilizing the circadian clock against phase shift and highlight it as a novel target for minimizing physiological disturbance in shift workers. |
