Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Retinal photoreceptors entrain the circadian system to the solar day. This photic resetting involves cAMP response element binding protein (CREB)-mediated upregulation of Per genes within individual cells of the suprachiasmatic nuclei (SCN). Our detailed understanding of this pathway is poor, and it remains unclear why entrainment to a new time zone takes several days. By analyzing the light-regulated transcriptome of the SCN, we have identified a key role for salt inducible kinase 1 (SIK1) and CREB-regulated transcription coactivator 1 (CRTC1) in clock re-setting. An entrainment stimulus causes CRTC1 to coactivate CREB, inducing the expression of Per1 and Sik1. SIK1 then inhibits further shifts of the clock by phosphorylation and deactivation of CRTC1. Knockdown of Sik1 within the SCN results in increased behavioral phase shifts and rapid re-entrainment following experimental jet lag. Thus SIK1 provides negative feedback, acting to suppress the effects of light on the clock. This pathway provides a potential target for the regulation of circadian rhythms.

Original publication

DOI

10.1016/j.cell.2013.08.004

Type

Journal article

Journal

Cell

Publication Date

29/08/2013

Volume

154

Pages

1100 - 1111

Keywords

Active Transport, Cell Nucleus, Animals, Circadian Clocks, Circadian Rhythm, Cyclic AMP Response Element-Binding Protein, Gene Knockdown Techniques, Mice, Mice, Inbred C57BL, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Rod Opsins, Signal Transduction, Suprachiasmatic Nucleus, Transcription Factors, Transcription, Genetic