The molecular mechanism of circadian rhythms

The endogenous and ubiquitous circadian rhythms (CR) are not understood in molecular terms, in spite of recent interesting advances. They concern, on one hand, protein synthesis, of which a small fraction--possibly a single protein--, formed on cytosolic ribosomes, may be required on each 24 h cycle. On the other hand, the per gene, involved in the control of CR in drosophila has been found to direct the synthesis of 2 (or 3) proteoglycans. Several models have been put forward in order to explain CR generation. Considering the complexity of the cell's organization and the occurrence of partial arrhythmicity, CR generation might result from the integration of a few physiological and metabolic pathways normally involving at least one feed-back loop. Sequentiality would be inherent to the kinetics of both the metabolic pathways and translocators located in the membranes of the various compartments; as a consequence, the peaks of the oscillatory activities would be positioned at particular phase points relative to others. Proteoglycans (or other proteins modified post-transcriptionally) could be involved in the operation of rhythms in controlling not only some plasmalemma (as proposed by Yu et al., 1987) but also intracellular membranes. Finally, reversible enzyme modification occurring on each 24 h cycle could be critically important in circadian rhythms generation.