Abstract
Circadian clocks impose daily periodicities to animal behavior and physiology. At their core, circadian rhythms are produced by intracellular transcriptional/translational feedback loops (TTFL). TTFLs may be altered by extracellular signals whose actions are mediated intracellularly by calcium and cAMP. In mammals these messengers act directly on TTFLs via the calcium/cAMP-dependent transcription factor, CREB. In the fruit fly, Drosophila melanogaster, calcium and cAMP also regulate the periodicity of circadian locomotor activity rhythmicity, but whether this is due to direct actions on the TTFLs themselves or are a consequence of changes induced to the complex interrelationship between different classes of central pacemaker neurons is unclear. Here we investigated this question focusing on the peripheral clock housed in the non-neuronal prothoracic gland (PG), which, together with the central pacemaker in the brain, controls the timing of adult emergence. We show that genetic manipulations that increased and decreased the levels of calcium and cAMP in the PG caused, respectively, a shortening and a lengthening of the periodicity of emergence. Importantly, knockdown of CREB in the PG caused an arrhythmic pattern of eclosion. Interestingly, the same manipulations directed at central pacemaker neurons caused arrhythmicity of eclosion and of adult locomotor activity, suggesting a common mechanism. Our results reveal that the calcium and cAMP pathways can alter the functioning of the clock itself. In the PG, these messengers, acting as outputs of the clock or as second messengers for stimuli external to the PG, could also contribute to the circadian gating of adult emergence.
Highlights
Circadian clocks impose a daily rhythmicity to the behavior and physiology of multicellular organisms
translational feedback loops (TTFL) may be altered by extracellular signals whose actions are mediated intracellularly by calcium and cAMP
In Drosophila, calcium and cAMP levels affect the periodicity of Drosophila circadian rhythms, but whether this is due to direct actions on the TTFLs themselves or is a consequence of changes induced to the complex interrelationship between different classes of central pacemaker neurons is unclear
Summary
Circadian clocks impose a daily rhythmicity to the behavior and physiology of multicellular organisms. The circadian system consists of a principal circadian pacemaker located in the central nervous system (CNS) as well as of autonomous circadian pacemakers located in most peripheral tissues. At their core, circadian rhythms are produced by intracellular transcriptional/translational feedback loops (TTFL) [1,2], and coordination at different levels ensures that the organism express a unified circadian time. Central and peripheral clocks are coordinated, maintaining a stable phase relationship In mammals this is accomplished through a variety of channels that are still poorly understood, and which include electrical, endocrine, metabolic, and even thermal signaling [17]. In mammals the liver clock can be entrained by daily feeding, which retains a phase difference with the central clock once restricted feeding ends [21]
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