Kinetics of doubletime kinase-dependent degradation of the Drosophila period protein

Sheyum Syed, Lino Saez, Michael W. Young

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Robust circadian oscillations of the proteins PERIOD (PER) and TIMELESS (TIM) are hallmarks of a functional clock in the fruit fly Drosophila melanogaster. Early morning phosphorylation of PER by the kinase Doubletime (DBT) and subsequent PER turnover is an essential step in the functioning of the Drosophila circadian clock. Here using time-lapse fluorescence microscopy we study PER stability in the presence of DBT and its short, long, arrhythmic, and inactive mutants in S2 cells. We observe robust PER degradation in a DBT allele-specific manner. With the exception of doubletime-short (DBT S), all mutants produce differential PER degradation profiles that show direct correspondence with their respective Drosophila behavioral phenotypes. The kinetics of PER degradation with DBT S in cell culture resembles that with wild-type DBT and posits that, in flies DBT S likely does not modulate the clock by simply affecting PER degradation kinetics. For all the other tested DBT alleles, the study provides a simple model in which the changes in Drosophila behavioral rhythms can be explained solely by changes in the rate of PER degradation.

Original languageEnglish (US)
Pages (from-to)27654-27662
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number31
DOIs
StatePublished - Aug 5 2011
Externally publishedYes

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Drosophila
Phosphotransferases
Diptera
Degradation
Kinetics
Clocks
Alleles
Circadian Clocks
Drosophila melanogaster
Fluorescence Microscopy
Fruit
Cell Culture Techniques
Phosphorylation
Fluorescence microscopy
Phenotype
Fruits
Cell culture
Drosophila PER protein
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Kinetics of doubletime kinase-dependent degradation of the Drosophila period protein. / Syed, Sheyum; Saez, Lino; Young, Michael W.

In: Journal of Biological Chemistry, Vol. 286, No. 31, 05.08.2011, p. 27654-27662.

Research output: Contribution to journalArticle

Syed, Sheyum ; Saez, Lino ; Young, Michael W. / Kinetics of doubletime kinase-dependent degradation of the Drosophila period protein. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 31. pp. 27654-27662.
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