A Model for Circadian Rhythms in Drosophila Incorporating the Formation of a Complex between the PER and TIM Proteins

Journal of Biological Rhythms - Tập 13 Số 1 - Trang 70-87 - 1998
Jean‐Christophe Leloup1, Albert Goldbeter2
1Unité de Chronobiologie Théorique des Sciences, Faculté des Sciences, Université Libre de Bruxelles, Campus Plaine, Brussels, Belgium.
2Unite de Chronobiologie theorique, Faculte des Sciences, Universite Libre de Bruxelles, Campus Plaine, C.P. 231, B-1050 Brussels, Belgium.

Tóm tắt

The authors present a model for circadian oscillations of the Period (PER) and Timeless (TIM) proteins in Drosophila. The model for the circadian clock is based on multiple phosphorylation of PER and TIM and on the negative feedback exerted by a nuclear PER-TIM complex on the transcription of the perand tim genes. Periodic behavior occurs in a large domain of parameter space in the form of limit cycle oscillations. These sustained oscillations occur in conditions corresponding to continuous darkness or to entrainment by light-dark cycles and are in good agreement with experimental observations on the temporal variations of PER and TIM and of per and tim mRNAs. Birhythmicity (coexistence of two periodic regimes) and aperiodic oscillations (chaos) occur in a restricted range of parameter values. The results are compared to the predictions of a model based on the sole regulation by PER. Both the formation of a complex between PER and TIM and protein phosphorylation are found to favor oscillatory behavior. Determining how the period depends on several key parameters allows us to test possible molecular explanations proposed for the altered period in the perl and pers mutants. The extended model further allows the construction of phase-response curves based on the light-induced triggering of TIM degradation. These curves, established as a function of both the duration and magnitude of the effect of a light pulse, match the phase-response curves obtained experimentally in the wild type and pers mutant of Drosophila.

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Journal of Biological Rhythms

Tập 13 Số 1

70-87

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