Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 312 (5781): 1809-1812

Copyright © 2006 by the American Association for the Advancement of Science

JETLAG Resets the Drosophila Circadian Clock by Promoting Light-Induced Degradation of TIMELESS

Kyunghee Koh, Xiangzhong Zheng, Amita Sehgal*

Abstract: Organisms ranging from bacteria to humans synchronize their internal clocks to daily cycles of light and dark. Photic entrainment of the Drosophila clock is mediated by proteasomal degradation of the clock protein TIMELESS (TIM). We have identified mutations in jetlag—a gene coding for an F-box protein with leucine-rich repeats—that result in reduced light sensitivity of the circadian clock. Mutant flies show rhythmic behavior in constant light, reduced phase shifts in response to light pulses, and reduced light-dependent degradation of TIM. Expression of JET along with the circadian photoreceptor cryptochrome (CRY) in cultured S2R cells confers light-dependent degradation onto TIM, thereby reconstituting the acute response + of the circadian clock to light in a cell culture system. Our results suggest that JET is essential for resetting the clock by transmitting light signals from CRY to TIM.

Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed. E-mail: amita{at}mail.med.upenn.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ramshackle (Brwd3) promotes light-induced ubiquitylation of Drosophila Cryptochrome by DDB1-CUL4-ROC1 E3 ligase complex.
N. Ozturk, S. J. VanVickle-Chavez, L. Akileswaran, R. N. Van Gelder, and A. Sancar (2013)
PNAS 110, 4980-4985
   Abstract »    Full Text »    PDF »
Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology.
X. Sun, E. H. A. Rikkerink, W. T. Jones, and V. N. Uversky (2013)
PLANT CELL 25, 38-55
   Abstract »    Full Text »    PDF »
CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila.
W. Luo, Y. Li, C.-H. A. Tang, K. C. Abruzzi, J. Rodriguez, S. Pescatore, and M. Rosbash (2012)
Genes & Dev. 26, 2536-2549
   Abstract »    Full Text »    PDF »
The Ability to Entrain to Long Photoperiods Differs between 3 Drosophila melanogaster Wild-Type Strains and Is Modified by Twilight Simulation.
D. Rieger, N. Peschel, V. Dusik, S. Glotz, and C. Helfrich-Forster (2012)
J Biol Rhythms 27, 37-47
   Abstract »    Full Text »    PDF »
HSP90 functions in the circadian clock through stabilization of the client F-box protein ZEITLUPE.
T.-s. Kim, W. Y. Kim, S. Fujiwara, J. Kim, J.-Y. Cha, J. H. Park, S. Y. Lee, and D. E. Somers (2011)
PNAS 108, 16843-16848
   Abstract »    Full Text »    PDF »
Post-Translational Regulation and Nuclear Entry of TIMELESS and PERIOD Are Affected in New timeless Mutant.
T. Hara, K. Koh, D. J. Combs, and A. Sehgal (2011)
J. Neurosci. 31, 9982-9990
   Abstract »    Full Text »    PDF »
Light-regulated interactions with SPA proteins underlie cryptochrome-mediated gene expression.
C. Fankhauser and R. Ulm (2011)
Genes & Dev. 25, 1004-1009
   Abstract »    Full Text »    PDF »
A CRY to Rise.
S. Hee Im and P. H. Taghert (2011)
Science 331, 1394-1395
   Abstract »    Full Text »    PDF »
CRYPTOCHROME Is a Blue-Light Sensor That Regulates Neuronal Firing Rate.
K. J. Fogle, K. G. Parson, N. A. Dahm, and T. C. Holmes (2011)
Science 331, 1409-1413
   Abstract »    Full Text »    PDF »
Reaction mechanism of Drosophila cryptochrome.
N. Ozturk, C. P. Selby, Y. Annayev, D. Zhong, and A. Sancar (2011)
PNAS 108, 516-521
   Abstract »    Full Text »    PDF »
The COP9 Signalosome Is Required for Light-Dependent Timeless Degradation and Drosophila Clock Resetting.
A. Knowles, K. Koh, J.-T. Wu, C.-T. Chien, D. A. Chamovitz, and J. Blau (2009)
J. Neurosci. 29, 1152-1162
   Abstract »    Full Text »    PDF »
A Drosophila model for Angelman syndrome.
Y. Wu, F. V. Bolduc, K. Bell, T. Tully, Y. Fang, A. Sehgal, and J. A. Fischer (2008)
PNAS 105, 12399-12404
   Abstract »    Full Text »    PDF »
The Blue-Light Photoreceptor CRYPTOCHROME Is Expressed in a Subset of Circadian Oscillator Neurons in the Drosophila CNS.
J. Benito, J. H. Houl, G. W. Roman, and P. E. Hardin (2008)
J Biol Rhythms 23, 296-307
   Abstract »    PDF »
Identification of novel genes involved in light-dependent CRY degradation through a genome-wide RNAi screen.
S. Sathyanarayanan, X. Zheng, S. Kumar, C.-H. Chen, D. Chen, B. Hay, and A. Sehgal (2008)
Genes & Dev. 22, 1522-1533
   Abstract »    Full Text »    PDF »
A systematic forward genetic analysis identified components of the Chlamydomonas circadian system.
T. Matsuo, K. Okamoto, K. Onai, Y. Niwa, K. Shimogawara, and M. Ishiura (2008)
Genes & Dev. 22, 918-930
   Abstract »    Full Text »    PDF »
Probing the Relative Importance of Molecular Oscillations in the Circadian Clock.
X. Zheng and A. Sehgal (2008)
Genetics 178, 1147-1155
   Abstract »    Full Text »    PDF »
Animal Type 1 Cryptochromes: ANALYSIS OF THE REDOX STATE OF THE FLAVIN COFACTOR BY SITE-DIRECTED MUTAGENESIS.
N. Ozturk, S.-H. Song, C. P. Selby, and A. Sancar (2008)
J. Biol. Chem. 283, 3256-3263
   Abstract »    Full Text »    PDF »
Rhythm Defects Caused by Newly Engineered Null Mutations in Drosophila's cryptochrome Gene.
E. Dolezelova, D. Dolezel, and J. C. Hall (2007)
Genetics 177, 329-345
   Abstract »    Full Text »    PDF »
The 2006 Pittendrigh/Aschoff Lecture: New Roles for Old Proteins in the Drosophila Circadian Clock.
P. Meyer and M. W. Young (2007)
J Biol Rhythms 22, 283-290
   Abstract »    PDF »
Targeted Degradation of PSEUDO-RESPONSE REGULATOR5 by an SCFZTL Complex Regulates Clock Function and Photomorphogenesis in Arabidopsis thaliana.
T. Kiba, R. Henriques, H. Sakakibara, and N.-H. Chua (2007)
PLANT CELL 19, 2516-2530
   Abstract »    Full Text »    PDF »
Functional Role of CREB-Binding Protein in the Circadian Clock System of Drosophila melanogaster.
C. Lim, J. Lee, C. Choi, J. Kim, E. Doh, and J. Choe (2007)
Mol. Cell. Biol. 27, 4876-4890
   Abstract »    Full Text »    PDF »
Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1).
Y. Fang, S. Sathyanarayanan, and A. Sehgal (2007)
Genes & Dev. 21, 1506-1518
   Abstract »    Full Text »    PDF »
The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period.
S. I. H. Godinho, E. S. Maywood, L. Shaw, V. Tucci, A. R. Barnard, L. Busino, M. Pagano, R. Kendall, M. M. Quwailid, M. R. Romero, et al. (2007)
Science 316, 897-900
   Abstract »    Full Text »    PDF »
Biological Rhythms Workshop IA: Molecular Basis of Rhythms Generation.
S. R. Mackey (2007)
Cold Spring Harb Symp Quant Biol 72, 7-19
   Abstract »    PDF »
Structure and Function of Animal Cryptochromes.
N. Ozturk, S.-H. Song, S. Ozgur, C. P. Selby, L. Morrison, C. Partch, D. Zhong, and A. Sancar (2007)
Cold Spring Harb Symp Quant Biol 72, 119-131
   Abstract »    PDF »
Posttranslational Control of the Neurospora Circadian Clock.
J. Cha, G. Huang, J. Guo, and Y. Liu (2007)
Cold Spring Harb Symp Quant Biol 72, 185-191
   Abstract »    PDF »
Posttranslational Photomodulation of Circadian Amplitude.
D. E. Somers, S. Fujiwara, W.-Y. Kim, and S.-S. Suh (2007)
Cold Spring Harb Symp Quant Biol 72, 193-200
   Abstract »    PDF »
Principles and Problems Revolving Round Rhythm-related Genetic Variants.
J. C. Hall, D. C. Chang, and E. Dolezelova (2007)
Cold Spring Harb Symp Quant Biol 72, 215-232
   Abstract »    PDF »
Genetics and Neurobiology of Circadian Clocks in Mammals.
S. M. Siepka, S.-H. Yoo, J. Park, C. Lee, and J. S. Takahashi (2007)
Cold Spring Harb Symp Quant Biol 72, 251-259
   Abstract »    PDF »
Molecular Analysis of Sleep: Wake Cycles in Drosophila.
A. Sehgal, W. Joiner, A. Crocker, K. Koh, S. Sathyanarayanan, Y. Fang, M. Wu, J. A. Williams, and X. Zheng (2007)
Cold Spring Harb Symp Quant Biol 72, 557-564
   Abstract »    PDF »
Timeless genes and jetlag.
R. N. Van Gelder (2006)
PNAS 103, 17583-17584
   Full Text »    PDF »
Veela defines a molecular link between Cryptochrome and Timeless in the light-input pathway to Drosophila's circadian clock.
N. Peschel, S. Veleri, and R. Stanewsky (2006)
PNAS 103, 17313-17318
   Abstract »    Full Text »    PDF »
Regulating a Circadian Clock's Period, Phase and Amplitude by Phosphorylation: Insights from Drosophila.
K. Bae and I. Edery (2006)
J. Biochem. 140, 609-617
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882