Originally published as Genetics Published Articles Ahead of Print on October 28, 2008.

Genetics, Vol. 181, 139-152, January 2009, Copyright © 2009
doi:10.1534/genetics.108.094805

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

Jin-Yuan Fan, Fabian Preuss¹, Michael J. Muskus, Edward S. Bjes and Jeffrey L. Price²

School of Biological Sciences, Division of Molecular Biology and Biochemistry, University of Missouri, Kansas City, Missouri 64110

² Corresponding author: School of Biological Sciences, Division of Molecular Biology and Biochemistry, University of Missouri–Kansas City, 5100 Rockhill Rd., Kansas City, MO 64110.
E-mail: pricejL{at}umkc.edu

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 article establish that the Drosophila dbt mutations have similar effects on period (PER) protein 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 the circadian period differently. The results demonstrate a high degree of evolutionary conservation of fly and vertebrate CKI and of the functions affected by their period-shortening mutations.

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Genetics 2009 181: NP. [Full Text]  

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