Unconventional Oscillations, Alternative Clocks

AKT is a protein kinase that conveys extracellular signals to regulate key cellular functions. Previous studies in mice identified daily rhythmicity in active AKT (pAKT) with elevated levels in the fed state. However, it is still unknown whether rhythmic AKT activation can be driven through intrinsic mechanisms.

Here, we inspected daily levels of pAKT, both in cultured cells and animal models. Unexpectedly, we found that neither environmental cues nor the circadian clock are necessary for pAKT rhythms, which exhibited free-running phosphorylation cycles with ultradian periodicity. We also performed liver transcriptome analysis and revealed ultradian rhythms in clock disrupted mice, corresponding to pAKT rhythmicity and consisting of AKT-related genes and regulators (PLOS Biology, 2021 December 30).

Overall, our findings uncover temporal regulation of AKT activation and reveal molecular rhythmicity that is independent of the canonical circadian clock. We are further looking for a) additional clock-independent rhythms; b) potential function consequences of these rhythms on the animal’s well-being; and c) mechanistic insights into the alternative oscillator clockwork.