Abstract
BackgroundA large number of organisms have internal circadian clocks that enable them to adapt to the cyclic changes of the external environment. In the model organism Drosophila melanogaster, feedback loops of transcription and translation are believed to be crucial for the maintenance of the central pacemaker. In this mechanism the cycle (or bmal1) gene, which is constitutively expressed, plays a critical role activating the expression of genes that will later inhibit their own activity, thereby closing the loop. Unlike Drosophila, the molecular clock of insect vectors is poorly understood, despite the importance of circadian behavior in the dynamic of disease transmission.ResultsHere we describe the sequence, genomic organization and circadian expression of cycle in the crepuscular/nocturnal hematophagous sandfly Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. Deduced amino acid sequence revealed that sandfly cycle has a C-terminal transactivation domain highly conserved among eukaryotes but absent in D. melanogaster. Moreover, an alternative form of the transcript was also identified. Interestingly, while cycle expression in Drosophila and other Diptera is constitutive, in sandflies it is rhythmic in males and female heads but constitutive in the female body. Blood-feeding, which causes down-regulation of period and timeless in this species, does not affect cycle expression.ConclusionSequence and expression analysis of cycle in L. longipalpis show interesting differences compared to Drosophila suggesting that hematophagous vector species might present interesting new models to study the molecular control of insect circadian clocks.
Highlights
A large number of organisms have internal circadian clocks that enable them to adapt to the cyclic changes of the external environment
The core clocks are generated by two negative feedback loops that are interconnected to the same two positive basic helix-loop-helix/PAScontaining transcription factors CLOCK (CLK) and CYCLE (CYC)(reviewed in [1,2])
The core clock molecules are relatively conserved between mammals and D. melanogaster, there are some interesting differences in, for example, the transcriptional control of Clk and cyc expression
Summary
A large number of organisms have internal circadian clocks that enable them to adapt to the cyclic changes of the external environment. In the model organism Drosophila melanogaster, feedback loops of transcription and translation are believed to be crucial for the maintenance of the central pacemaker. In this mechanism the cycle (or bmal1) gene, which is constitutively expressed, plays a critical role activating the expression of genes that will later inhibit their own activity, thereby closing the loop. Whereas VRI represses Clk production just after lights off, PDP1ε activates it in the middle of the night, separating the phases of Clk transcription and repression [3,4] These oscillations of gene expression and posttranslational regulation are necessary for the robustness and accuracy of overt physiological and behavioral rhythms. Its ability to bind E-boxes and activate transcription in a cyclic manner resides in its phosphorylation pattern, with only the late day/early night hypophosphorylated forms being capable of promoting per and tim expression [12,13]
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