A role for CK2 in the Drosophila circadian oscillator

Nat Neurosci. 2003 Mar;6(3):251-7. doi: 10.1038/nn1007.

Abstract

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.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Biological Clocks / physiology*
  • Casein Kinase II
  • Circadian Rhythm / physiology*
  • Dimerization
  • Drosophila Proteins*
  • Drosophila melanogaster / physiology*
  • Insect Proteins / metabolism
  • Motor Activity / physiology
  • Mutation
  • Neurons / cytology
  • Neurons / metabolism
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • Phenotype
  • Protein Binding / physiology
  • Protein Subunits / genetics
  • Protein Subunits / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*

Substances

  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • Protein Subunits
  • tim protein, Drosophila
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases