Photic signaling by cryptochrome in the Drosophila circadian system

Oscillations of the period (per) and timeless (tim) gene products are an in tegral part of the feedback loop that underlies circadian behavioral rhythm s in Drosophila melanogaster. Resetting this loop in response to light requ ires the putative circadian photoreceptor cryptochrome (CRY). We dissected the early events in photic resetting by determining the mechanisms underlyi ng the CRY response to light and by investigating the relationship between CRY and the light-induced ubiquitination of the TIM protein. In response to light, CRY is degraded by the proteasome through a mechanism that requires electron transport. Various CRY mutant proteins are not degraded, and this suggests that an intramolecular conversion is required for this light resp onse. Light-induced TIM ubiquitination precedes CRY degradation and is incr eased when electron transport is blocked. Thus, inhibition of electron tran sport may "lock" CRY in an active state by preventing signaling required ei ther to degrade CRY or to convert it to an inactive form. High levels of CR Y block TIM ubiquitination, suggesting a mechanism by which light-driven ch anges in CRY could control TIM ubiquitination.