title: A PER/TIM/DBT interval timer for Drosophila's circadian clock.
abstract: Circadian rhythms in Drosophila are supported by a negative feedback loop, in which PERIOD (PER) and Timeless (TIM) shut down their own transcription as they translocate once a day from the cytoplasm of clock-containing cells to the nucleus. Period length is partially determined by an interval of cytoplasmic retention of the TIM and PER proteins. To study this process, we examined PER/TIM/Doubletime (DBT) physical interactions and nuclear translocation by imaging individual cultured Drosophila cells. Using live cell video microscopy and green fluorescent protein (GFP) tags, we observed dynamic patterns of stability and localization for DBT, PER, and TIM that resembled those previously found in vivo. These studies suggest that a cytoplasmic interval timer regulates nuclear translocation of these proteins. The cultured cell assay provides a potent system to study interactions among new and known genes involved in the generation of circadian behavior.
authors.affiliation: Laboratory of Genetics, The Rockefeller University, New York, New York 10021, USA.
authors.forename: L
authors.initials: L
authors.lastname: Saez
authors.forename: P
authors.initials: P
authors.lastname: Meyer
authors.forename: M W
authors.initials: MW
authors.lastname: Young
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D048149:Casein Kinase 1 epsilon / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D025461:Feedback, Physiological; D017344:Genes, Insect; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D056950:Period Circadian Proteins
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C113519:dco protein, Drosophila; C096445:tim protein, Drosophila; D048149:Casein Kinase 1 epsilon