Figure 9
Light-driven signalling to the circadian clock via ROS, the MAPK cascade and the D-box enhancer in vertebrate cells. Schematic representation of how exposure to blue light differentially influences MAPK signalling and D-box enhancer-driven gene expression. In all three cell lines studied, blue light exposure triggers an increase in intracellular ROS levels. In PAC-2 cells (central panel), this results in two peaks of activation of p38 and JNK, one rapid (5–15 mins) and a second delayed increase (6–7 hours). In contrast, levels of P-ERK remain relatively unchanged during light exposure. This combined signalling results in the activation of D-box-driven gene expression, ultimately leading to circadian clock entrainment (indicated by green arrow). In HeLa cells (left panel), all three MAP kinases are activated with a predominantly delayed response (6–7 hours) that does not influence D-box driven transcription. Indeed, in mammalian cells D-box regulated expression constitutes a clock output pathway (indicated by white arrow). In EPA cells (right panel), all three MAP kinases are activated rapidly and transiently (with p38 also exhibiting the second, delayed peak of activation). However, as for the HeLa cells, this signalling does not affect the D-box enhancer or entrain the circadian clock. Indeed, it has been previously shown28 that cavefish cells possess a blind circadian clock (indicated by a red cross)
