Rhythmic Protein Condensation in the Circadian Regulation of Glycogen Metabolism

Circadian rhythms are endogenously generated daily cycles in physiology that are closely tied to metabolism and can be found in all kingdoms of life. In cyanobacteria, energy storage through glycogen metabolism is highly rhythmic, but the underlying mechanisms remain unclear. I report that we find that the glycogen synthase enzyme, GlgA, is rhythmically condensed during growth in constant light. The appearance of condensed foci of GlgA corresponds to inhibition of glycogen synthesis during the morning hours, and reduced enzyme activity can be induced with crowding agents in vitro. Through mutational analysis, we show that the condensation status of GlgA is dictated by the state of the circadian clock rather than the amount of glycogen in the cell. These results reveal a model of circadian control of glycogen metabolism achieved through rhythmic spatial reorganization of a key enzyme.