cAMP-dependent signaling as a core component of the mammalian circadian pacemaker
Open accessAbstract
The mammalian circadian clockwork is modeled as transcriptional and posttranslational feedback loops, whereby circadian genes are periodically suppressed by their protein products. We show that adenosine 3',5'-monophosphate (cAMP) signaling constitutes an additional, bona fide component of the oscillatory network. cAMP signaling is rhythmic and sustains the transcriptional loop of the suprachiasmatic nucleus, determining canonical pacemaker properties of amplitude, phase, and period. This role is general and is evident in peripheral mammalian tissues and cell lines, which reveals an unanticipated point of circadian regulation in mammals qualitatively different from the existing transcriptional feedback model. We propose that daily activation of cAMP signaling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles.
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cAMP is not solely an output of the SCN, but an integral component of the SCN pacemaker, regulating transcriptional cycles.
“O'Neill et al. [43] showed that cAMP is not solely an output of the SCN, but an integral component of the SCN pacemaker, regulating transcriptional cycles.”
From Circadian control of glucose metabolism (2014) · cites this paper as [43]
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- Authors
- O'Neill, J. S., Maywood, E. S., Chesham, J. E., Takahashi, J. S., & Hastings, M. H.
- Affiliations
- Northwestern University (US)
- Corresponding author
- O'Neill, John S.
- Hastings, Michael H.
- ORCID
- Venue
- Science
- Published
- 2008-05-16
- Volume
- 320
- Issue
- 5878
- Pages
- 949-953
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2735813
- OpenAlex
- W2027704011
- Cited by
- 418
- References
- 28
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 13 · 2023: 12 · 2022: 17 · 2021: 15 · 2020: 28 · 2019: 17 · 2018: 19 · 2017: 15 · 2016: 22 · 2015: 25 · 2014: 39 · 2013: 31 · 2012: 33
- FWCI
- 16.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Physical Sciences › Computer Science › Computer Networks and Communications › Nonlinear Dynamics and Pattern Formation
- Keywords
- cAMP signaling, circadian clock, circadian pacemaker, suprachiasmatic nucleus, transcriptional feedback loop, circadian rhythm
- MeSH terms
- Adenylyl Cyclase Inhibitors, Adenine, Cyclic AMP, Adenylyl Cyclases, Animals, Biological Clocks, Circadian Rhythm, Enzyme Inhibitors, Gene Expression Regulation, Mice, Transgenic, Nuclear Proteins, Suprachiasmatic Nucleus, Transcription Factors, Transcription, Genetic, Signal Transduction, Cell Cycle Proteins, Response Elements, Guanine Nucleotide Exchange Factors, Feedback, Physiological, NIH 3T3 Cells, Mice, Period Circadian Proteins
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