Even though daily temperature fluctuations serve as a synchronizing signal for circadian clocks (see above), clocks are also temperature compensated. This means that when kept under constant conditions (i.e., no daily fluctuations of either light/dark or temperature), circadian clocks tick at the same speed at low or high constant temperatures.
This is quite a remarkable feature, because (a) temperature cycles do influence the clock (see above), and (b) biochemical reactions usually occur at a faster rate at higher temperatures. Temperature compensation is even more remarkable when considering poikilotherm animals like Drosophila, who adjust their body temperature with that of the environment. Of course it is crucial that circadian clocks are temperature compensated, because a clock that runs with different speed at different temperatures would not be a clock (rather a thermometer). Despite this fascinating feature, the molecular mechanisms underlying temperature compensation are not understood in any system. In Drosophila several models have been put forward that implicate temperature-dependent inter- and intra-molecular interactions between key clock proteins as crucial part of this mechanism. Recently, we identified a region within the Period protein that disrupts temperature compensation when altered. Similarly, we could show that a different region of this clock protein is important for the formation of a Per:Per homodimer (Figure) and reveal its function within the circadian clock mechanism (Landskron et al., 2009). Following similar approaches, we are now determining the potential effects on protein:protein interactions mediated by the temperature compensation defective Per protein we identified. Our preliminary data lead to a hypothesis whereby temperature-dependent protein interactions between different clock proteins (e.g., Per and Tim) influence the rates of nuclear import and export of these proteins. Because the nuclear concentrations of Per and Tim influence the transcription rate of their own RNA, temperature-controlled nuclear-cytoplasmic shuttling could represent a basic principle of temperature compensation, at least in Drosophila.