FIGURE 2.

Circadian clocks impose a daily rhythm on intracellular Ca²⁺ signaling. (A) Photic inputs via CRY or other signaling molecules such as PLC cause a phase-shift in the expression of molecular clock components in the mammalian and Drosophila central clocks. In turn, TTFL regulate cytosolic Ca²⁺ rhythms. In SCN neurons, circadian oscillations of Ca²⁺ levels are also dependent on the mobilization of Ca²⁺ from the endoplasmic reticulum. (B) Circadian clocks impose a daily rhythm of expression to a large number of components of the Ca²⁺ signaling pathway by acting at transcriptional or post-transcriptional levels (including by regulating alternative splicing in Drosophila and microRNA in mice). In addition, in mice, the Ca²⁺/calcineurin/NFAT pathway exhibits a rhythmic activity in peripheral clocks, such as the one present in skeletal muscle or heart, which is probably mediated by inputs from the central clock. IP₃R, inositol 1,4,5-triphosphate Receptor; NFAT, nuclear factor of activated T-cells; RORE, ROR response elements. RCAN1, regulator of calcineurin 1. RyR, ryanodine receptor. SERCA, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase. See Figure 1 for other abbreviations.