The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.

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...

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Principais autores: Jagannath, A, Butler, R, Godinho, S, Couch, Y, Brown, L, Vasudevan, SR, Flanagan, K, Anthony, D, Churchill, G, Wood, M, Steiner, G, Ebeling, M, Hossbach, M, Wettstein, J, Duffield, G, Gatti, S, Hankins, M, Foster, R, Peirson, S
Formato: Journal article
Idioma:English
Publicado em: 2013
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author Jagannath, A
Butler, R
Godinho, S
Couch, Y
Brown, L
Vasudevan, SR
Flanagan, K
Anthony, D
Churchill, G
Wood, M
Steiner, G
Ebeling, M
Hossbach, M
Wettstein, J
Duffield, G
Gatti, S
Hankins, M
Foster, R
Peirson, S
author_facet Jagannath, A
Butler, R
Godinho, S
Couch, Y
Brown, L
Vasudevan, SR
Flanagan, K
Anthony, D
Churchill, G
Wood, M
Steiner, G
Ebeling, M
Hossbach, M
Wettstein, J
Duffield, G
Gatti, S
Hankins, M
Foster, R
Peirson, S
author_sort Jagannath, A
collection OXFORD
description 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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spelling oxford-uuid:82c0f7ad-beb5-402b-913d-f9bf48b01b002022-03-26T21:39:38ZThe CRTC1-SIK1 pathway regulates entrainment of the circadian clock.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:82c0f7ad-beb5-402b-913d-f9bf48b01b00EnglishSymplectic Elements at Oxford2013Jagannath, AButler, RGodinho, SCouch, YBrown, LVasudevan, SRFlanagan, KAnthony, DChurchill, GWood, MSteiner, GEbeling, MHossbach, MWettstein, JDuffield, GGatti, SHankins, MFoster, RPeirson, SRetinal 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.
spellingShingle Jagannath, A
Butler, R
Godinho, S
Couch, Y
Brown, L
Vasudevan, SR
Flanagan, K
Anthony, D
Churchill, G
Wood, M
Steiner, G
Ebeling, M
Hossbach, M
Wettstein, J
Duffield, G
Gatti, S
Hankins, M
Foster, R
Peirson, S
The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.
title The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.
title_full The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.
title_fullStr The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.
title_full_unstemmed The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.
title_short The CRTC1-SIK1 pathway regulates entrainment of the circadian clock.
title_sort crtc1 sik1 pathway regulates entrainment of the circadian clock
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