Intracellular Ca2+ regulates free-running circadian clock oscillation in vivo

J Neurosci. 2007 Nov 14;27(46):12489-99. doi: 10.1523/JNEUROSCI.3680-07.2007.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biological Clocks / genetics*
  • Calcium / metabolism*
  • Calcium Signaling / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Calmodulin / metabolism
  • Cells, Cultured
  • Circadian Rhythm / genetics*
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation / genetics
  • Intracellular Fluid / metabolism
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Nervous System / cytology
  • Nervous System / metabolism
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Neurons / metabolism
  • Parvalbumins / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Calmodulin
  • Drosophila Proteins
  • Parvalbumins
  • Transcription Factors
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium