JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS.
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.
Koh
Kyunghee
K
Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Zheng
Xiangzhong
X
Sehgal
Amita
A
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured; D002940:Circadian Rhythm; D056931:Cryptochromes; D004330:Drosophila / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D005136:Eye Proteins / Q000378:metabolism; D044783:F-Box Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D005260:Female; D008027:Light; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D019076:Transgenes; D025801:Ubiquitin / Q000378:metabolism
D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D044783:F-Box Proteins; C511696:JET protein, Drosophila; D043562:Receptors, G-Protein-Coupled; D025801:Ubiquitin; C119828:cry protein, Drosophila; C096445:tim protein, Drosophila