Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.

Cyanobacteria are the only model circadian clock system in which a circadian oscillator can be reconstituted in vitro. The underlying circadian mechanism appears to comprise two subcomponents: a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO and...

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Autores principales:	Ximing Qin, Mark Byrne, Yao Xu, Tetsuya Mori, Carl Hirschie Johnson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/40ce54c8611a4b248b6f837c6d9edc60
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spelling	oai:doaj.org-article:40ce54c8611a4b248b6f837c6d9edc602021-12-02T19:54:48ZCoupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.1544-91731545-788510.1371/journal.pbio.1000394https://doaj.org/article/40ce54c8611a4b248b6f837c6d9edc602010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20563306/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Cyanobacteria are the only model circadian clock system in which a circadian oscillator can be reconstituted in vitro. The underlying circadian mechanism appears to comprise two subcomponents: a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO and TTFL have been hypothesized to operate as dual oscillator systems in cyanobacteria. However, we find that they have a definite hierarchical interdependency-the PTO is the core pacemaker while the TTFL is a slave oscillator that quickly damps when the PTO stops. By analysis of overexpression experiments and mutant clock proteins, we find that the circadian system is dependent upon the PTO and that suppression of the PTO leads to damped TTFL-based oscillations whose temperature compensation is not stable under different metabolic conditions. Mathematical modeling indicates that the experimental data are compatible with a core PTO driving the TTFL; the combined PTO/TTFL system is resilient to noise. Moreover, the modeling indicates a mechanism by which the TTFL can feed into the PTO such that new synthesis of clock proteins can phase-shift or entrain the core PTO pacemaker. This prediction was experimentally tested and confirmed by entraining the in vivo circadian system with cycles of new clock protein synthesis that modulate the phosphorylation status of the clock proteins in the PTO. In cyanobacteria, the PTO is the self-sustained core pacemaker that can operate independently of the TTFL, but the TTFL damps when the phosphorylation status of the PTO is clamped. However, the TTFL can provide entraining input into the PTO. This study is the first to our knowledge to experimentally and theoretically investigate the dynamics of a circadian clock in which a PTO is coupled to a TTFL. These results have important implications for eukaryotic clock systems in that they can explain how a TTFL could appear to be a core circadian clockwork when in fact the true pacemaker is an embedded biochemical oscillator.Ximing QinMark ByrneYao XuTetsuya MoriCarl Hirschie JohnsonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 8, Iss 6, p e1000394 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ximing Qin Mark Byrne Yao Xu Tetsuya Mori Carl Hirschie Johnson Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.
description	Cyanobacteria are the only model circadian clock system in which a circadian oscillator can be reconstituted in vitro. The underlying circadian mechanism appears to comprise two subcomponents: a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO and TTFL have been hypothesized to operate as dual oscillator systems in cyanobacteria. However, we find that they have a definite hierarchical interdependency-the PTO is the core pacemaker while the TTFL is a slave oscillator that quickly damps when the PTO stops. By analysis of overexpression experiments and mutant clock proteins, we find that the circadian system is dependent upon the PTO and that suppression of the PTO leads to damped TTFL-based oscillations whose temperature compensation is not stable under different metabolic conditions. Mathematical modeling indicates that the experimental data are compatible with a core PTO driving the TTFL; the combined PTO/TTFL system is resilient to noise. Moreover, the modeling indicates a mechanism by which the TTFL can feed into the PTO such that new synthesis of clock proteins can phase-shift or entrain the core PTO pacemaker. This prediction was experimentally tested and confirmed by entraining the in vivo circadian system with cycles of new clock protein synthesis that modulate the phosphorylation status of the clock proteins in the PTO. In cyanobacteria, the PTO is the self-sustained core pacemaker that can operate independently of the TTFL, but the TTFL damps when the phosphorylation status of the PTO is clamped. However, the TTFL can provide entraining input into the PTO. This study is the first to our knowledge to experimentally and theoretically investigate the dynamics of a circadian clock in which a PTO is coupled to a TTFL. These results have important implications for eukaryotic clock systems in that they can explain how a TTFL could appear to be a core circadian clockwork when in fact the true pacemaker is an embedded biochemical oscillator.
format	article
author	Ximing Qin Mark Byrne Yao Xu Tetsuya Mori Carl Hirschie Johnson
author_facet	Ximing Qin Mark Byrne Yao Xu Tetsuya Mori Carl Hirschie Johnson
author_sort	Ximing Qin
title	Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.
title_short	Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.
title_full	Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.
title_fullStr	Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.
title_full_unstemmed	Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.
title_sort	coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/40ce54c8611a4b248b6f837c6d9edc60
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Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system.

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