PMID:17068124

Citation	Peschel, N, Veleri, S and Stanewsky, R (2006) Veela defines a molecular link between Cryptochrome and Timeless in the light-input pathway to Drosophila's circadian clock. Proc. Natl. Acad. Sci. U.S.A. 103:17313-8
Abstract	Organisms use the daily cycles of light and darkness to synchronize their internal circadian clocks with the environment. Because they optimize physiological processes and behavior, properly synchronized circadian clocks are thought to be important for the overall fitness. In Drosophila melanogaster, the circadian clock is synchronized with the natural environment by light-dependent degradation of the clock protein Timeless, mediated by the blue-light photoreceptor Cryptochrome (Cry). Here we report identification of a genetic variant, Veela, which severely disrupts this process, because these genetically altered flies maintain behavioral and molecular rhythmicity under constant-light conditions that usually stop the clock. We show that the Veela strain carries a natural timeless allele (ls-tim), which encodes a less-light-sensitive form of Timeless in combination with a mutant variant of the F-box protein Jetlag. However, neither the ls-tim nor the jetlag genetic variant alone is sufficient to disrupt light input into the central pacemaker. We show a strong interaction between Veela and cryptochrome genetic variants, demonstrating that the Jetlag, Timeless, and Cry proteins function in the same pathway. Veela also reveals a function for the two natural variants of timeless, which differ in their sensitivity to light. In combination with the complex array of retinal and extraretinal photoreceptors known to signal light to the pacemaker, this previously undescribed molecular component of photic sensitivity mediated by the two Timeless proteins reveals that an unexpectedly rich complexity underlies modulation of this process.
Links	PubMed PMC1859927 Online version:10.1073/pnas.0606675103
Keywords	Alleles; Amino Acid Sequence; Animals; Animals, Genetically Modified; Circadian Rhythm/physiology; Cryptochromes; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; F-Box Proteins/chemistry; F-Box Proteins/genetics; F-Box Proteins/metabolism; Flavoproteins/genetics; Flavoproteins/metabolism; Light; Molecular Sequence Data; Motor Activity; Mutation/genetics; Neuroglia/metabolism; Neurons/metabolism; Polymorphism, Genetic/genetics; Renin/metabolism; Sequence Alignment; Signal Transduction
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