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The Journal of Neuroscience, November 14, 2007, 27(46):12489-12499; doi:10.1523/JNEUROSCI.3680-07.2007

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Cellular/Molecular
Intracellular Ca2+ Regulates Free-Running Circadian Clock Oscillation In Vivo

Marie C. Harrisingh,1 Ying Wu,1 Gregory A. Lnenicka,2 and Michael N. Nitabach1

1Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06520, and 2Department of Biological Sciences, University at Albany, Albany, New York 12222

Correspondence should be addressed to Michael N. Nitabach, Department of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520. Email: michael.nitabach{at}yale.edu

Although circadian oscillation in dynamics of intracellular Ca2+ signals has been observed in both plant and animal cells, it has remained unknown whether Ca2+ signals play an in vivo role in cellular oscillation itself. To address this question, we modified the dynamics of intracellular Ca2+ signals in circadian pacemaker neurons in vivo by targeted expression of varying doses of a Ca2+ buffer protein in transgenic Drosophila melanogaster. Intracellular Ca2+ buffering in pacemaker neurons results in dose-dependent slowing of free-running behavioral rhythms, with average period >3 h longer than control at the highest dose. The rhythmic nuclear accumulation of a transcription factor known to be essential for cellular circadian oscillation is also slowed. We also determined that Ca2+ buffering interacts synergistically with genetic manipulations that interfere with either calmodulin or calmodulin-dependent protein kinase II function. These results suggest a role for intracellular Ca2+ signaling in regulating intrinsic cellular oscillation in vivo.

Key words: Ca2+; circadian rhythm; Drosophila; calmodulin; CaMKII; transcription


Received Aug. 13, 2007; revised Oct. 1, 2007; accepted Oct. 3, 2007.

Correspondence should be addressed to Michael N. Nitabach, Department of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520. Email: michael.nitabach{at}yale.edu




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