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

Mutations lowering the kinase activity of Drosophila Doubletime (DBT) and vertebrate casein kinase I[straight epsilon]/δ (CKI[straight epsilon]/δ) produce long-period, short-period, and arrhythmic circadian rhythms. Since most ckI short-period mutants have been isolated in mammals, while the long-pe...

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Bibliographic Details
Published in:Genetics (Austin) 2009, Vol.181 (1), p.139-152
Main Authors: Fan, Jin-Yuan, Preuss, Fabian, Muskus, Michael J, Bjes, Edward S, Price, Jeffrey L
Format: Article
Language:English
Subjects:
autophosphorylation
casein kinase
Cell cycle
Circadian rhythm
Drosophila melanogaster
E coli
enzyme activity
insect proteins
Kinases
mutants
PER protein
period phosphorylation
phenotype
protein kinases
protein phosphorylation
Proteins
vertebrates
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Summary:Mutations lowering the kinase activity of Drosophila Doubletime (DBT) and vertebrate casein kinase I[straight epsilon]/δ (CKI[straight epsilon]/δ) 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[straight epsilon]/δ. Moreover, expression of either Drosophila DBT or the vertebrate CKIδ kinase carrying the Drosophila dbt^sup S^ or vertebrate tau mutations in all circadian cells leads to short-period circadian rhythms. By contrast, vertebrate CKIδ carrying the dbt^sup L^ mutation does not lengthen circadian rhythms, while Drosophila DBT^sup L^ does. Different effects of the dbt^sup 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 CKIδ and of the functions affected by their period-shortening mutations. [PUBLICATION ABSTRACT]
ISSN:0016-6731
1943-2631