A role for casein kinase 2alpha in the Drosophila circadian clock.
Circadian clocks drive rhythmic behaviour in animals and are regulated by transcriptional feedback loops. For example, the Drosophila proteins Clock (Clk) and Cycle (Cyc) activate transcription of period (per) and timeless (tim). Per and Tim then associate, translocate to the nucleus, and repress the activity of Clk and Cyc. However, post-translational modifications are also critical to proper timing. Per and Tim undergo rhythmic changes in phosphorylation, and evidence supports roles for two kinases in this process: Doubletime (Dbt) phosphorylates Per, whereas Shaggy (Sgg) phosphorylates Tim. Yet Sgg and Dbt often require a phosphoserine in their target site, and analysis of Per phosphorylation in dbt mutants suggests a role for other kinases. Here we show that the catalytic subunit of Drosophila casein kinase 2 (CK2alpha) is expressed predominantly in the cytoplasm of key circadian pacemaker neurons. CK2alpha mutant flies show lengthened circadian period, decreased CK2 activity, and delayed nuclear entry of Per. These effects are probably direct, as CK2alpha specifically phosphorylates Per in vitro. We propose that CK2 is an evolutionary link between the divergent circadian systems of animals, plants and fungi.
Lin
Jui-Ming
JM
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Kilman
Valerie L
VL
Keegan
Kevin
K
Paddock
Brie
B
Emery-Le
Myai
M
Rosbash
Michael
M
Allada
Ravi
R
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001683:Biological Clocks; D015153:Blotting, Western; D047390:Casein Kinase II; D002467:Cell Nucleus / Q000378:metabolism; D002940:Circadian Rhythm; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D019476:Insect Proteins / Q000378:metabolism; D009043:Motor Activity; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D056950:Period Circadian Proteins; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C096445:tim protein, Drosophila; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases