Intracellular Ca2+ regulates free-running circadian clock oscillation in vivo.
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.
Harrisingh
Marie C
MC
Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Wu
Ying
Y
Lnenicka
Gregory A
GA
Nitabach
Michael N
MN
D000818:Animals; D030801:Animals, Genetically Modified; D001683:Biological Clocks / Q000235:genetics*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D007424:Intracellular Fluid / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009420:Nervous System / Q000166:cytology / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010320:Parvalbumins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002147:Calmodulin; D029721:Drosophila Proteins; D010320:Parvalbumins; D014157:Transcription Factors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium