PDP1ε Functions Downstream of the Circadian Oscillator to Mediate Behavioral Rhythms

Mar 9, 2007The Journal of neuroscience : the official journal of the Society for Neuroscience

PDP1epsilon acts after the body clock to control daily behavior patterns

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Abstract

Reducing PDP1epsilon levels in clock cells by approximately 70% does not alter Clk mRNA cycling or circadian oscillator function.

The circadian oscillator is regulated by feedback loops involving period/timeless and Clock proteins.
VRI and PDP1epsilon proteins bind the same regulatory element, influencing Clk transcription levels.
Constant low or high levels of PDP1epsilon disrupt locomotor activity rhythms while maintaining normal circadian oscillator function in brain neurons.
PDP1epsilon is not essential for the activation of Clk, suggesting it may regulate the output of the circadian oscillator.

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The Drosophila circadian oscillator is composed of autoregulatory period/timeless (per/tim) and Clock (Clk) feedback loops that control rhythmic transcription. In the Clk loop, CLOCK-CYCLE heterodimers activate vrille (vri) and PAR domain protein 1epsilon (Pdp1epsilon) transcription, then sequential repression by VRI and activation by PDP1epsilon mediate rhythms in Clk transcription. Because VRI and PDP1epsilon bind the same regulatory element, the VRI/PDP1epsilon ratio is thought to control the level of Clk transcription. Thus, constant high or low PDP1epsilon levels in clock cells should eliminate Clk mRNA cycling and disrupt circadian oscillator function. Here we show that reducing PDP1epsilon levels in clock cells by approximately 70% via RNA interference or increasing PDP1epsilon levels by approximately 10-fold in clock cells does not alter Clk mRNA cycling or circadian oscillator function. However, constant low or high PDP1epsilon levels in clock cells disrupt locomotor activity rhythms despite persistent circadian oscillator function in brain pacemaker neurons that extend morphologically normal projections into the dorsal brain. These results demonstrate that the VRI/PDP1epsilon ratio neither controls Clk mRNA cycling nor circadian oscillator function and argue that PDP1epsilon is not essential for Clk activation. PDP1epsilon is nevertheless required for behavioral rhythmicity, which suggests that it functions to regulate oscillator output.

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PDP1ε Functions Downstream of the Circadian Oscillator to Mediate Behavioral Rhythms

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