The circadian clock component PERIOD2: from molecular to cerebral functions

The circadian clock is based on a molecular oscillator, which simulates the external day within nearly all of a body's cells. This "internalized" day then defines activity and rest phases for the cells and the organism by generating precise rhythms in the metabolism, physiology, and behavior. In its perfect state, this timing system allows for the synchronization of an organism to its environment and this may optimize energy handling and responses to daily recurring challenges. However, nowadays, we believe that desynchronization of an organism due to its lifestyle or problems with its circadian clock not only causes discomfort but also may aggravate conditions such as depression, metabolic syndrome, addiction, or cancer. In this review, we focus on one simple cogwheel of the mammalian circadian clock, the PERIOD2 (PER2) protein. Originally identified as an integral part of the molecular mechanism that yields overt rhythms of about 24h, more recently multiple other functions have been identified. In essence, the PER proteins, in addition to their important function within the molecular oscillator, can be seen not only as integrators on the input side of the circadian clock but also as mediators of clock output. This diversity in their function is possible, because the PER proteins can interact with a multitude of other proteins transferring oscillator timing information to the latter. In this fashion, the circadian clock synchronizes many rhythmic processes.