Abstract
SummaryThe daily changes of light and dark exemplify a prominent cue for the synchronization of internal circadian clocks to external time. The match between external and internal time is crucial for the fitness of organisms and desynchronization has been linked to numerous physical and mental health problems in humans. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila both the visual system and dedicated non-image forming photoreceptors contribute to light resetting of the circadian clock. In the fruit fly, light-dependent degradation of the clock protein TIMELESS (TIM) by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the visual system also contributes. In order to understand the nature of the visual system contribution, we generated a genetic variant exhibiting extremely slow phototransduction kinetics, yet normal sensitivity. We show that in this variant the visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular synchronization to light:dark cycles. This function depends on an alternative Phospholipase C-ß enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting by light. We show that this pathway requires the ubiquitin ligase CULLIN-3, presumably mediating CRY-independent degradation of TIM during light:dark cycles. Our results suggest that visual system contribution to circadian clock entrainment operates on a drastically slower time scale compared with fast, visual and image forming phototransduction. Our findings are therefore consistent with the general idea that the visual system samples light over prolonged periods of time (hours) in order to reliably synchronize their internal clocks with the external time.
Publisher
Cold Spring Harbor Laboratory