Dominant-negative CK2α induces potent effects on circadian rhythmicity

Elaine M. Smith, Jui Ming Lin, Rose Anne Meissner, Ravi Allada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Circadian clocks organize the precise timing of cellular and behavioral events. In Drosophila, circadian clocks consist of negative feedback loops in which the clock component PERIOD (PER) represses its own transcription. PER phosphorylation is a critical step in timing the onset and termination of this feedback. The protein kinase CK2 has been linked to circadian timing, but the importance of this contribution is unclear; it is not certain where and when CK2 acts to regulate circadian rhythms. To determine its temporal and spatial functions, a dominant negative mutant of the catalytic alpha subunit, CK2αTik, was targeted to circadian neurons. Behaviorally, CK2αTik induces severe period lengthening (∼33 h), greater than nearly all known circadian mutant alleles, and abolishes detectable free-running behavioral rhythmicity at high levels of expression. CK2αTik, when targeted to a subset of pacemaker neurons, generates period splitting, resulting in flies exhibiting both long and near 24-h periods. These behavioral effects are evident even when CK2αTik expression is induced only during adulthood, implicating an acute role for CK2α function in circadian rhythms. CK2αTik expression results in reduced PER phosphorylation, delayed nuclear entry, and dampened cycling with elevated trough levels of PER. Heightened trough levels of per transcript accompany increased protein levels, suggesting that CK2αTik disturbs negative feedback of PER on its own transcription. Taken together, these in vivo data implicate a central role of CK2α function in timing PER negative feedback in adult circadian neurons.

Original languageEnglish (US)
Pages (from-to)99-109
Number of pages11
JournalPLoS genetics
Volume4
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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