FRQ-CK1 Interaction Underlies Temperature Compensation of the Circadian Clock.

Temperature compensation is a fundamental property of all circadian clocks; temperature compensation results in a relatively constant period length at different physiological temperatures, but its mechanism is unclear. Formation of a stable complex between clock proteins and casein kinase 1 (CK1) is a conserved feature in eukaryotic circadian mechanisms. Here, we show that the FRQ-CK1 interaction and CK1-mediated FRQ phosphorylation, not FRQ stability, are main mechanisms responsible for the circadian temperature compensation phenotypes in . Inhibition of CK1 kinase activity impaired the temperature compensation profile. Importantly, both the loss of temperature compensation and temperature overcompensation phenotypes of the wild-type and different clock mutant strains can be explained by temperature-dependent alterations of the FRQ-CK1 interaction. Furthermore, mutations that were designed to specifically affect the FRQ-CK1 interaction resulted in impaired temperature compensation of the clock. Together, these results reveal the temperature-compensated FRQ-CK1 interaction, which results in temperature-compensated CK1-mediated FRQ and WC phosphorylation, as a main biochemical process that underlies the mechanism of circadian temperature compensation in . Temperature compensation allows clocks to adapt to all seasons by having a relatively constant period length at different physiological temperatures, but the mechanism of temperature compensation is unclear. Stability of clock proteins was previously proposed to be a major factor that regulated temperature compensation. In this study, we showed that the interaction between CK1 and FRQ, but not FRQ stability, explains the circadian temperature compensation phenotypes in . This study uncovered the key biochemical mechanism responsible for temperature compensation of the circadian clock and further established the mechanism for period length determination in . Because the regulation of circadian clock proteins by CK1 and the formation of a stable clock complex with CK1 are highly conserved in eukaryotic clocks, a similar mechanism may also exist in animal clocks.