title: A proposal for temperature compensation of the circadian rhythm in Drosophila based on dimerization of the per protein.
abstract: Recently Goldbeter suggested an interesting model of circadian rhythms based on feedback inhibition by the PER protein on its own rate of transcription. In his model, the long delay necessary for generating 24 h periodicity is associated with slow phosphorylations of PER protein in the cytoplasm, assuming that only highly phosphorylated forms of PER are able to enter the nucleus and there interfere with transcription of the per gene. By casting this molecular mechanism in mathematical form, Goldbeter showed that it is consistent with many known features of circadian oscillations in PER abundance. However, he did not address one of the most important characteristics of the circadian rhythm: the near constancy of the 24 h period over a broad temperature range. Huang, Curtin, and Rosbash have recently suggested that dimerization of the PER protein is involved in temperature compensation of the circadian rhythm in Drosophila, because in mutant flies lacking the PER dimerization domain, the period is strongly dependent on temperature. We incorporate this idea into Goldbeter's model by introducing parallel pathways of phosphorylation of PER monomers and dimers. We assume that both monomers and dimers can be transported into the nucleus as long as at least one PER subunit is multiply phosphorylated. Temperature compensation in our model arises from opposing effects of temperature (T) on the rate of association of PER monomers and the rate of nuclear import of PER protein. In mutant flies, when PER subunits cannot dimerize, the period of the oscillation increases with T, so we assume that the rate constant for nuclear import is a decreasing function of T. To compensate for this effect in wild-type flies, we assume that the rate of association of PER subunits is an increasing function of T. The mathematical model reveals the relationship between these opposing tendencies that must be satisfied to achieve effective temperature compensation.
authors.affiliation: Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061-0406, USA.
authors.forename: C I
authors.initials: CI
authors.lastname: Hong
authors.forename: J J
authors.initials: JJ
authors.lastname: Tyson
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D019281:Dimerization; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins; D007700:Kinetics; D008954:Models, Biological; D009687:Nuclear Proteins / Q000096:biosynthesis*; D056950:Period Circadian Proteins; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins