p38 MAP Kinase Regulates Circadian Rhythms in Drosophila

Nov 19, 2014Journal of biological rhythms

p38 MAP kinase controls daily biological rhythms in fruit flies

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Abstract

Drosophila mutants in p38Kb exhibit either arrhythmicity or longer free-running circadian periods as they age.

p38Kb is expressed in clock neurons and is implicated in regulating circadian rhythms.
Optimal function of p38Kb is necessary for normal free-running circadian rhythms.
Mutants and transgenic modifications of p38Kb result in similar alterations in rhythmic behavior.
p38Kb interacts with the period gene, affecting both period length and rhythmicity strength.
Manipulation of p38K signaling influences the expression of MNK/Lk6, which cycles with the circadian clock.

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The large repertoire of circadian rhythms in diverse organisms depends on oscillating central clock genes, input pathways for entrainment, and output pathways for controlling rhythmic behaviors. Stress-activated p38 MAP Kinases (p38K), although sparsely investigated in this context, show circadian rhythmicity in mammalian brains and are considered part of the circadian output machinery in Neurospora. We find that Drosophila p38Kb is expressed in clock neurons, and mutants in p38Kb either are arrhythmic or have a longer free-running periodicity, especially as they age. Paradoxically, similar phenotypes are observed through either transgenic inhibition or activation of p38Kb in clock neurons, suggesting a requirement for optimal p38Kb function for normal free-running circadian rhythms. We also find that p38Kb genetically interacts with multiple downstream targets to regulate circadian locomotor rhythms. More specifically, p38Kb interacts with the period gene to regulate period length and the strength of rhythmicity. In addition, we show that p38Kb suppresses the arrhythmic behavior associated with inhibition of a second p38Kb target, the transcription factor Mef2. Finally, we find that manipulating p38K signaling in free-running conditions alters the expression of another downstream target, MNK/Lk6, which has been shown to cycle with the clock and to play a role in regulating circadian rhythms. These data suggest that p38Kb may affect circadian locomotor rhythms through the regulation of multiple downstream pathways.

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p38 MAP Kinase Regulates Circadian Rhythms in Drosophila

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