Rhythmic protein condensation in the circadian regulation of glycogen metabolism

节律性蛋白质凝聚在糖原代谢昼夜节律调控中的作用

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Abstract

Circadian rhythms are endogenously generated daily cycles in physiology that are closely tied to metabolism and can be found in all kingdoms of life. Because of their genetic simplicity, cyanobacteria provide a unique opportunity to uncover rhythmic mechanisms. In cyanobacteria, glycogen storage is highly rhythmic. Using a combination of mass spectrometry and live cell imaging, we find that the glycogen synthase enzyme (GlgA), is rhythmically condensed. The appearance of condensed foci of GlgA corresponds to inhibition of glycogen synthesis during morning hours, allowing storage to be coordinated with the demand for energy at dusk. 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.

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