Functional Analysis of Mammalian Cryptochromes: a matter of time

We live in a clockwork universe – dictated by the particular configuration of our solar system, such as the movements of planets and gravity. The annual rotation of the Earth around the Sun is the primary cause of seasonal fluctuations in temperatures, whereas the Earth’s rotation around its axis causes daily alterations in temperature and light conditions. Other phenomena, such as tides, are influenced by the monthly revolution of the Moon around the Earth. As one complete rotation of the Earth takes 24 hours, all living organisms have adapted by evolving their own internal clockwork tuned to a 24-hour day/night cycle to adapt their behaviour, physiology and metabolism. Circadian rhythms, as their name indicates (“circadian” comes from the Latin circa, meaning “around” and dies, meaning “a day”), are endogenous rhythms with a period of about 24 hours that regulate all aspects of the physiology of most organisms (e.g. blood pressure, body temperature, hormonal levels), behaviour (e.g. alertness, sleep cycle) and metabolism (Gachon et al., 2004; Lowrey et al., 2004; Reppert and Weaver, 2001). These internal clocks are reset to light/dark cycles and other daily external cues known as zeitgebers (German meaning time-givers), and therefore circadian rhythms are synchronized with the external environment. In mammals, the light is the major zeitgeber for circadian rhythms (Dijk et al., 1995). In rodents, circadian rhythms of wheel-running activity are presented by doubleplotted actograms (Figure 1). When environmental cues are eliminated by moving organism to constant darkness, the circadian clock is no longer reset each day and its endogenous periodicity, called free-running period, is revealed and can be determined. As light is the major zeitgeber of the circadian clock it can reset the clock in accordance with the phase response curve (PRC). The PRC illustrates the relationship between the timing and the effect of a treatment designed to affect the circadian clock. Depending on the timing, light can advance or delay the circadian rhythm. Exposure to bright light early or late in the subjective night induces phase delay or phase advance of the circadian clock, respectively (Daan and Pittendrigh, 1976).