Veela defines a molecular link between Cryptochrome and Timeless in the light-input pathway to Drosophila's circadian clock
- *Institute of Zoology, University of Regensburg, Universitätsstrasse 31, 93040 Regensburg, Germany; and
- ‡School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom
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Edited by Jeffrey C. Hall, Brandeis University, Waltham, MA, and approved September 7, 2006 (received for review August 4, 2006)
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.
Footnotes
- §To whom correspondence should be addressed. E-mail: r.stanewsky{at}qmul.ac.uk
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Author contributions: N.P. and S.V. contributed equally to this work; R.S. designed research; N.P., S.V., and R.S. performed research; N.P., S.V., and R.S. analyzed data; and N.P. and R.S. wrote the paper. The authors declare no conflict of interest.
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↵ †Present address: National Institutes of Health, Building 35, 9000 Rockville Pike, Bethesda, MD 20892.
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The authors declare no conflict of interest.
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This article is a PNAS direct submission.
- Abbreviations:
- LD,
- light/dark;
- LL,
- constant light;
- Cry,
- Cryptochrome;
- Per,
- Period;
- Tim,
- Timeless;
- LN,
- lateral neurons;
- DN,
- dorsal neurons;
- l-LNv,
- large LN;
- LRR,
- leucine-rich repeat;
- ZT,
- Zeitgeber time.
- © 2006 by The National Academy of Sciences of the USA
