Approximately daily, or circadian, rhythms are ubiquitous across eukaryotes. They are manifest in the temporal co-ordination of metabolism, physiology and behaviour, thereby allowing organisms to anticipate and synchronize with daily environmental cycles. Although cellular rhythms are self-sustained and cell-intrinsic, in mammals, the master regulator of timekeeping is localized within the hypothalamic SCN (suprachiasmatic nucleus). Molecular models for mammalian circadian rhythms have focused largely on transcriptional–translational feedback loops, but recent data have revealed essential contributions by intracellular signalling mechanisms. cAMP and Ca2+ signalling are not only regulated by the cellular clock, but also contribute directly to the timekeeping mechanism, in that appropriate manipulations determine the canonical pacemaker properties of amplitude, phase and period. It is proposed that daily auto-amplification of second messenger activity, through paracrine neuropeptidergic coupling, is necessary and sufficient to account for the increased amplitude, accuracy and robustness of SCN timekeeping.
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Conference Article| January 19 2012
The essential role of cAMP/Ca2+ signalling in mammalian circadian timekeeping
John S. O'Neill;
John S. O'Neill 1
1Department of Clinical Neurosciences, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, U.K.
1To whom correspondence should be addressed (email firstname.lastname@example.org).
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Akhilesh B. Reddy
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John S. O'Neill, Akhilesh B. Reddy; The essential role of cAMP/Ca2+ signalling in mammalian circadian timekeeping. Biochem Soc Trans 1 February 2012; 40 (1): 44–50. doi: https://doi.org/10.1042/BST20110691
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