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Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
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CaMKII is essential for the cellular clock and coupling between morning and evening behavioral rhythms
Naohiro Kon1, Tomoko Yoshikawa2, Sato Honma2
1Department of Biosciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan;
Genes & Development
|May 17, 2014
Summary
Calcium/calmodulin-dependent protein kinase II (CaMKII) is crucial for mammal circadian rhythms. CaMKII activity synchronizes internal biological clocks and maintains daily activity patterns.
Area of Science:
- Neuroscience
- Chronobiology
- Molecular Biology
Background:
- Mammalian daily behavioral rhythms are controlled by the suprachiasmatic nucleus (SCN) central circadian clock.
- Robust SCN oscillation relies on calcium (Ca2+), but the molecular mechanism is unclear.
- SCN oscillations involve coupled morning and evening oscillators maintaining stable activity patterns.
Purpose of the Study:
- To investigate the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in SCN cellular oscillation and synchronization.
- To elucidate the molecular mechanism by which CaMKII influences circadian rhythmicity.
Main Methods:
- Utilized a kinase-dead mutation in mouse CaMKIIα to assess its impact on behavioral rhythms and SCN function.
- Performed cellular and biochemical analyses to examine CaMKII signaling pathways.
- Investigated the effect of CaMKII on CLOCK and BMAL1 dimerization and E-box-dependent gene expression.
Main Results:
- CaMKII activity is essential for both SCN cellular oscillation and inter-oscillator synchronization.
- A kinase-dead CaMKIIα mutation impaired behavioral rhythmicity and caused decoupling of morning/evening activity rhythms.
- Mutant SCN showed uncoupled oscillations between the right and left nuclei.
- CaMKII signaling promotes CLOCK and BMAL1 dimerization, activating E-box-dependent gene expression.
Conclusions:
- CaMKII plays a dual role in the circadian system: as a component of the cell-autonomous clockwork and as a synchronizer of circadian activities.
- CaMKII is a key molecular link between Ca2+ signaling and the regulation of circadian behavior.
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