NEMO Kinase Contributes to Core Period Determination by Slowing the Pace of the Drosophila Circadian Oscillator

Apr 26, 2011Current biology : CB

NEMO kinase helps set the daily rhythm by slowing the internal clock in fruit flies

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Abstract

Knockdown of the proline-directed kinase nemo (nmo) shortens the circadian period in Drosophila.

nmo is identified as a novel component of the Drosophila circadian oscillator.
Both reduced nmo expression and a nmo hypomorphic mutant lead to a shorter circadian period.
Overexpression of nmo results in a longer circadian period.
Decreasing nmo levels in clock cells increases CLK levels, while overexpression decreases CLK levels and delays PER and TIM accumulation.
These findings suggest that nmo may influence the circadian rhythm by regulating the expression of CLK, PER, and TIM.

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The Drosophila circadian oscillator is comprised of transcriptional feedback loops that are activated by CLOCK (CLK) and CYCLE (CYC) and repressed by PERIOD (PER) and TIMELESS (TIM) [1]. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM [2-4]. Although kinases that control PER and TIM levels and subcellular localization have been identified [5-10], additional kinases are predicted to target PER, TIM, and/or CLK to promote time-specific transcriptional repression. We screened for kinases that alter circadian behavior via clock cell-directed RNA interference (RNAi) and identified the proline-directed kinase nemo (nmo) as a novel component of the circadian oscillator. Both nmo RNAi knockdown and a nmo hypomorphic mutant shorten circadian period, whereas nmo overexpression lengthens circadian period. CLK levels increase when nmo expression is knocked down in clock cells, whereas CLK levels decrease and PER and TIM accumulation are delayed when nmo is overexpressed in clock cells. These data suggest that nmo slows the pace of the circadian oscillator by altering CLK, PER, and TIM expression, thereby contributing to the generation of an ~24 hr circadian period.

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NEMO Kinase Contributes to Core Period Determination by Slowing the Pace of the Drosophila Circadian Oscillator

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