Drosophila and Vertebrate Casein Kinase I Exhibit Evolutionary Conservation of Circadian Function

Mutations lowering the kinase activity of Drosophila Doubletime (DBT) and vertebrate casein kinase I/ (CKI/) produce long-period, short-period and arrhythmic circadian rhythms. Since most ckI short-period mutants have been isolated in mammals, while the long-period mutants have been found mostly in 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 manuscript establish that the Drosophila dbt mutations have similar effects on PER phosphorylation by the fly and vertebrate enzymes in vitro, and that Drosophila DBT has an inhibitory C terminal domain and exhibits autophosphorylation, as does vertebrate CKI/. Moreover, expression of either Drosophila DBT or the vertebrate CKI kinase carrying the Drosophila dbt^S or vertebrate tau mutations in all circadian cells leads to short-period circadian rhythms. By contrast, vertebrate CKI carrying the dbt^L mutation does not lengthen circadian rhythms, while Drosophila DBT^L does. Different effects of the dbt^S and tau mutations on the oscillations of PER phosphorylation suggest that the mutations shorten circadian period differently. The results demonstrate a high degree of evolutionary conservation of fly and vertebrate CKI, and for the functions affected by their period-shortening mutations.

Key Words: biological clock, doubletime, period, protein phosphorylation, tau

Online ISS 1091-6490
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