THE CROSSTALK BETWEEN PHYSIOLOGY AND CIRCADIAN CLOCKPROTEINS

摘要

In mammals, many physiological processes present diurnal variations, and most ofthese rhythms persist even in absence of environmental timing cues. These endogenouscircadian rhythms are generated by intracellular timing mechanisms termed circadianclocks. In mammals, the master clock is located in the suprachiasmatic nuclei (SCN),but other brain regions and most peripheral tissues contain circadian clocks. Theseclocks are responsive to environmental cues, in particular light/dark and feeding/fasting cycles. In the last few years, tissue-specific knock-out and transgenic mousemodels have helped to define the physiological roles of specific clocks. Recent reportsindicate that the clock-physiology connection is bi-directional, and physiological cues,in particular the energetic status of the cell, can feed into the clockwork. This effect wasdiscovered unexpectedly in molecular analyses of clock protein modifications. Beyondthe positive and negative transcription/translation feedback loops of the molecularoscillator lies another level of complexity. Post-translational modifications of clock pro-teins are both critical for the timing of the clock feedback mechanism and to provideregulatory fine-tuning. This review summarizes recent advances in our understandingof the roles of peripheral clocks and of post-translational modifications occurring onclock proteins. These two matters are at the intersection of physiology, metabolism, andthe circadian system.