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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898689/ https://www.ncbi.nlm.nih.gov/pubmed/23993098 http://dx.doi.org/10.1016/j.cell.2013.08.004 |
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author | Jagannath, Aarti Butler, Rachel Godinho, Sofia I.H. Couch, Yvonne Brown, Laurence A. Vasudevan, Sridhar R. Flanagan, Kevin C. Anthony, Daniel Churchill, Grant C. Wood, Matthew J.A. Steiner, Guido Ebeling, Martin Hossbach, Markus Wettstein, Joseph G. Duffield, Giles E. Gatti, Silvia Hankins, Mark W. Foster, Russell G. Peirson, Stuart N. |
author_facet | Jagannath, Aarti Butler, Rachel Godinho, Sofia I.H. Couch, Yvonne Brown, Laurence A. Vasudevan, Sridhar R. Flanagan, Kevin C. Anthony, Daniel Churchill, Grant C. Wood, Matthew J.A. Steiner, Guido Ebeling, Martin Hossbach, Markus Wettstein, Joseph G. Duffield, Giles E. Gatti, Silvia Hankins, Mark W. Foster, Russell G. Peirson, Stuart N. |
author_sort | Jagannath, Aarti |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3898689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38986892014-01-24 The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock Jagannath, Aarti Butler, Rachel Godinho, Sofia I.H. Couch, Yvonne Brown, Laurence A. Vasudevan, Sridhar R. Flanagan, Kevin C. Anthony, Daniel Churchill, Grant C. Wood, Matthew J.A. Steiner, Guido Ebeling, Martin Hossbach, Markus Wettstein, Joseph G. Duffield, Giles E. Gatti, Silvia Hankins, Mark W. Foster, Russell G. Peirson, Stuart N. Cell Article 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. Cell Press 2013-08-29 /pmc/articles/PMC3898689/ /pubmed/23993098 http://dx.doi.org/10.1016/j.cell.2013.08.004 Text en © 2013 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Jagannath, Aarti Butler, Rachel Godinho, Sofia I.H. Couch, Yvonne Brown, Laurence A. Vasudevan, Sridhar R. Flanagan, Kevin C. Anthony, Daniel Churchill, Grant C. Wood, Matthew J.A. Steiner, Guido Ebeling, Martin Hossbach, Markus Wettstein, Joseph G. Duffield, Giles E. Gatti, Silvia Hankins, Mark W. Foster, Russell G. Peirson, Stuart N. 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898689/ https://www.ncbi.nlm.nih.gov/pubmed/23993098 http://dx.doi.org/10.1016/j.cell.2013.08.004 |
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