FIGURE 1.

Ca²⁺ signaling modulates the core components of the circadian clock. (A) In Drosophila and mammals, intracellular cytosolic Ca²⁺ rhythms are regulated by external signals such as light stimuli and neuropeptides. (B) In the SCN, external signals may affect the TTFL via the G_q-Ca²⁺ pathway. In turn, Ca²⁺ signaling via CREB and the regulation of the phosphorylation state (C) and proteasomal degradation (D) of clock proteins, orchestrate the effect of Ca²⁺ on the circadian clock in Drosophila and mammals. BMAL1, Brain and Muscle ARNT-Like 1, ortholog of Drosophila Cycle gene; CaMK, Ca²⁺/calmodulin-dependent protein kinase. CLOCK, Circadian Locomotor Output Cycles Kaput; CREB, cAMP response element-binding protein; CRE elements, cAMP response elements; CRY, cryptochrome; E-box, circadian enhancer box; ER, endoplasmic reticulum; PER, PERIOD protein; PKC, protein kinase C; ROR-α, retinoid-related orphan receptor alpha; TIM, TIMELESS protein.