Drosophila and Vertebrate Casein Kinase I delta Exhibits Evolutionary Conservation of Circadian Function

Mutations lowering the kinase activity of Drosophila Doubletime (DBT) and vertebrate casein kinase I epsilon/delta (CKI epsilon/delta) produce long-period, short-period, and arrhythmic circadian rhythms. Since most ckl short-period mutants have been isolated ill mammals, while the long-period Mutants have been found Mostly ill Drosophila, lowered kinase activity may have opposite consequences in flies and vertebrates, because of differences between the kinases or their circadian mechanisms. However, the results of this article establish that the Drosophila At Mutations have similar effects oil Period (PER) protein phosphorylation by the fly and vertebrate enzymes in vitro and that Drosophila DBT has all inhibitory C-terminal domain and exhibits autophosphorylation, as does vertebrate CKI epsilon/delta. Moreover, expression of either Drosophila DBT the vertebrate CKI delta kinase carrying the Drosophila dbt(s) or vertebrate tau Imitations in all circadian cells leads to short-period circadian rhythms. By contrast, vertebrate CKI delta carrying the dbt(L) Mutation does not lengthen circadian rhythms, while Drosophila DBTL does. Different effects of the dbt(s) and tau. mutations on the oscillations of PER phosphorylation suggest that the Mutations shorten the circadian period differently. The results demonstrate a high degree Of evolutionary conservation of fly and vertebrate CKI delta and of the functions affected by their period-shortening mutations.