The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock | Zendy

Aarti Jagannath | Zendy; Rachel Butler | Zendy; Sofia I.H. Godinho | Zendy; Yvonne Couch | Zendy; Laurence A. Brown | Zendy; Sridhar R. Vasudevan | Zendy; Kevin C. Flanagan | Zendy; Daniel C. Anthony | Zendy; Grant C. Churchill | Zendy; Matthew J. A. Wood | Zendy; Guido Steiner | Zendy; Martin Ebeling | Zendy; Markus Hoßbach | Zendy; Joseph G. Wettstein | Zendy; Giles E. Duffield | Zendy; Silvia Gatti | Zendy; Mark W. Hankins | Zendy; F. Foster | Zendy; Stuart N. Peirson | Zendy

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The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock

Author(s) -

Aarti Jagannath,

Rachel Butler,

Sofia I.H. Godinho,

Yvonne Couch,

Laurence A. Brown,

Sridhar R. Vasudevan,

Kevin C. Flanagan,

Daniel C. Anthony,

Grant C. Churchill,

Matthew J. A. Wood,

Guido Steiner,

Martin Ebeling,

Markus Hoßbach,

Joseph G. Wettstein,

Giles E. Duffield,

Silvia Gatti,

Mark W. Hankins,

F. Foster,

Stuart N. Peirson

Publication year - 2013

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2013.08.004

Subject(s) - biology , circadian clock , per1 , entrainment (biomusicology) , light effects on circadian rhythm , circadian rhythm , suprachiasmatic nucleus , creb , bacterial circadian rhythms , gene knockdown , microbiology and biotechnology , neuroscience , clock , transcription factor , genetics , medicine , rhythm , gene

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.

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