Photic signaling by cryptochrome in the Drosophila circadian system.
Oscillations of the period (per) and timeless (tim) gene products are an integral part of the feedback loop that underlies circadian behavioral rhythms in Drosophila melanogaster. Resetting this loop in response to light requires the putative circadian photoreceptor cryptochrome (CRY). We dissected the early events in photic resetting by determining the mechanisms underlying the CRY response to light and by investigating the relationship between CRY and the light-induced ubiquitination of the TIM protein. In response to light, CRY is degraded by the proteasome through a mechanism that requires electron transport. Various CRY mutant proteins are not degraded, and this suggests that an intramolecular conversion is required for this light response. Light-induced TIM ubiquitination precedes CRY degradation and is increased when electron transport is blocked. Thus, inhibition of electron transport may "lock" CRY in an active state by preventing signaling required either to degrade CRY or to convert it to an inactive form. High levels of CRY block TIM ubiquitination, suggesting a mechanism by which light-driven changes in CRY could control TIM ubiquitination.
Lin
F J
FJ
Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA.
Song
W
W
Meyer-Bernstein
E
E
Naidoo
N
N
Sehgal
A
A
D000818:Animals; D015153:Blotting, Western; D002940:Circadian Rhythm; D056931:Cryptochromes; D003546:Cysteine Endopeptidases; D004330:Drosophila; D029721:Drosophila Proteins; D004579:Electron Transport; D005136:Eye Proteins; D005420:Flavoproteins / Q000378:metabolism; D019476:Insect Proteins / Q000502:physiology; D008027:Light; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009154:Mutation; D009687:Nuclear Proteins / Q000502:physiology; D010084:Oxidation-Reduction; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism
D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D019476:Insect Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D043562:Receptors, G-Protein-Coupled; D025801:Ubiquitin; C119828:cry protein, Drosophila; C096445:tim protein, Drosophila; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex