Casein Kinase 1 Delta Regulates the Pace of the Mammalian Circadian Clock

May 6, 2009Molecular and cellular biology

Casein kinase 1 delta controls the speed of the mammal’s internal daily clock

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

CK1delta deficiency leads to a 2-hour longer circadian rhythm period.

Disruption of the CK1delta gene results in a nonfunctional protein and is associated with increased daytime levels of nuclear PER proteins.
Mice with liver-specific CK1delta disruption exhibit elevated levels of PER-CRY-CLOCK complexes.
In vitro studies show that the half-life of PER2 increases by approximately 20% in CK1delta-deficient conditions.
Fibroblast cultures from CK1delta-deficient embryos also demonstrate longer circadian rhythms.
In contrast, the disruption of CK1epsilon does not affect circadian rhythm parameters.

AI simplified

Both casein kinase 1 delta (CK1delta) and epsilon (CK1epsilon) phosphorylate core clock proteins of the mammalian circadian oscillator. To assess the roles of CK1delta and CK1epsilon in the circadian clock mechanism, we generated mice in which the genes encoding these proteins (Csnk1d and Csnk1e, respectively) could be disrupted using the Cre-loxP system. Cre-mediated excision of the floxed exon 2 from Csnk1d led to in-frame splicing and production of a deletion mutant protein (CK1delta(Delta2)). This product is nonfunctional. Mice homozygous for the allele lacking exon 2 die in the perinatal period, so we generated mice with liver-specific disruption of CK1delta. In livers from these mice, daytime levels of nuclear PER proteins, and PER-CRY-CLOCK complexes were elevated. In vitro, the half-life of PER2 was increased by approximately 20%, and the period of PER2::luciferase bioluminescence rhythms was 2 h longer than in controls. Fibroblast cultures from CK1delta-deficient embryos also had long-period rhythms. In contrast, disruption of the gene encoding CK1epsilon did not alter these circadian endpoints. These results reveal important functional differences between CK1delta and CK1epsilon: CK1delta plays an unexpectedly important role in maintaining the 24-h circadian cycle length.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text ↗

Casein Kinase 1 Delta Regulates the Pace of the Mammalian Circadian Clock

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief