A role for the PERIOD:PERIOD homodimer in the Drosophila circadian clock

PLoS Biology
Johannes LandskronRalf Stanewsky

Abstract

Circadian clocks in eukaryotes rely on transcriptional feedback loops, in which clock genes repress their own transcription resulting in molecular oscillations with a period of approximately 24 h. In Drosophila, the clock proteins Period (PER) and Timeless (TIM) operate in such a feedback loop, whereby they first accumulate in the cytoplasm of clock cells as a heterodimer. Nuclear translocation of the complex or the individual PER and TIM proteins is followed by repression of per and tim transcription, whereby PER seems to act as the prime repressor. We found that in addition to PER:TIM complexes, functional PER:PER homodimers exist in flies. Specific disruption of PER homodimers results in drastically impaired behavioral and molecular rhythmicity, pointing the biological importance of this clock protein complex. Analysis of PER subcellular distribution and repressor competence in the PER dimer mutant revealed defects in PER nuclear translocation and a disruption of rhythmic period transcription. The striking similarity of these phenotypes with that of reduced CKII activity suggests that the formation or function of the PER dimer is closely linked to this kinase. Our results confirm a previous structural model for PER and provi...Continue Reading

References

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Citations

Jun 7, 2014·Annual Review of Biochemistry·Brian R Crane, Michael W Young
Sep 17, 2009·Journal of Biological Rhythms·Valerie L Kilman, Ravi Allada
Aug 4, 2010·Journal of Biological Rhythms·Ralph Jürgen StelzerLars Chittka
Feb 6, 2013·Journal of Biological Rhythms·Pamela MenegazziRodolfo Costa
Aug 12, 2009·Journal of Neurochemistry·Changtaek ChoiJoonho Choe
Jun 6, 2013·Journal of Biological Rhythms·Yue Li, Michael Rosbash
Jun 11, 2011·The Journal of Biological Chemistry·Sheyum SyedMichael W Young
Aug 9, 2011·Essays in Biochemistry·Nicholas R J Glossop

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Methods Mentioned

BETA
nuclear translocation
transgenic
co-immunoprecipitation
CoIP
transgenics
gel filtration
in vivo
transfection
protein blots
X-ray

Software Mentioned

BRASS ( biological rhythms analysis
fly
MATLab
per
ImageJ

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