A role for CK2 in the Drosophila circadian oscillator.
The posttranslational modification of clock proteins is critical for the function of circadian oscillators. By genetic analysis of a Drosophila melanogaster circadian clock mutant known as Andante, which has abnormally long circadian periods, we show that casein kinase 2 (CK2) has a role in determining period length. Andante is a mutation of the gene encoding the beta subunit of CK2 and is predicted to perturb CK2beta subunit dimerization. It is associated with reduced beta subunit levels, indicative of a defect in alpha:beta association and production of the tetrameric alpha2:beta2 holoenzyme. Consistent with a direct action on the clock mechanism, we show that CK2beta is localized within clock neurons and that the clock proteins Period (Per) and Timeless (Tim) accumulate to abnormally high levels in the Andante mutant. Furthermore, the nuclear translocation of Per and Tim is delayed in Andante, and this defect accounts for the long-period phenotype of the mutant. These results suggest a function for CK2-dependent phosphorylation in the molecular oscillator.
Akten
Bikem
B
Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 01211, USA.
Jauch
Eike
E
Genova
Ginka K
GK
Kim
Eun Young
EY
Edery
Isaac
I
Raabe
Thomas
T
Jackson
F Rob
FR
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D047390:Casein Kinase II; D002940:Circadian Rhythm / Q000502:physiology*; D019281:Dimerization; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000502:physiology*; D019476:Insect Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D056950:Period Circadian Proteins; D010641:Phenotype; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology
D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D021122:Protein Subunits; C096445:tim protein, Drosophila; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases