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PMID: 17893330 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Drosophila DBT lacking protein kinase activity produces long-period and arrhythmic circadian behavioral and molecular rhythms.

Molecular and cellular biology ·Vol. 27 ·No. 23 ·2007-12-00 ·Pages 8049-64

Muskus MJ, Preuss F, Fan JY, Bjes ES, Price JL

Abstract

A mutation (K38R) which specifically eliminates kinase activity was created in the Drosophila melanogaster ckI gene (doubletime [dbt]). In vitro, DBT protein carrying the K38R mutation (DBT(K/R)) interacted with Period protein (PER) but lacked kinase activity. In cell culture and in flies, DBT(K/R) antagonized the phosphorylation and degradation of PER, and it damped the oscillation of PER in vivo. Overexpression of short-period, long-period, or wild-type DBT in flies produced the same circadian periods produced by the corresponding alleles of the endogenous gene. These mutations therefore dictate an altered "set point" for period length that is not altered by overexpression. Overexpression of the DBT(K/R) produced effects proportional to the titration of endogenous DBT, with long circadian periods at lower expression levels and arrhythmicity at higher levels. This first analysis of adult flies with a virtual lack of DBT activity demonstrates that DBT's kinase activity is necessary for normal circadian rhythms and that a general reduction of DBT kinase activity does not produce short periods.

MeSH Terms
Alleles Amino Acid Sequence Animals Arginine/genetics Behavior, Animal/physiology Casein Kinase 1 epsilon/chemistry,metabolism Catalysis Cell Nucleus/metabolism Circadian Rhythm/physiology Drosophila Proteins/chemistry,metabolism Drosophila melanogaster/enzymology Gene Expression Genes, Dominant Larva/cytology,metabolism Lysine/genetics Molecular Sequence Data Motor Activity/physiology Mutant Proteins/metabolism Nuclear Proteins/metabolism Period Circadian Proteins Phosphoproteins/metabolism Protein Binding Protein Kinases/metabolism Protein Processing, Post-Translational Time Factors
Chemicals
Drosophila Proteins Mutant Proteins Nuclear Proteins PER protein, Drosophila Period Circadian Proteins Phosphoproteins dco protein, Drosophila Arginine Protein Kinases Casein Kinase 1 epsilon Lysine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Muskus Michael J
School of Biological Sciences, University of Missouri-Kansas City, 5100 Rockhill Rd., Kansas City, MO 64110, USA.
Preuss Fabian
Fan Jin-Yuan
Bjes Edward S
Price Jeffrey L
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.00680-07
Published
2007-12-00
Epub
2007-00-24
Pages
8049-64
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2169192
Subset
IM
Grants
NIMH NIH HHS · R01 MH056895 · United States
External Links
PubMed source DOI: 10.1128/MCB.00680-07 PMC Full Text View journal details
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