A conserved chronobiological complex timesC. elegansdevelopment

The mammalian PAS-domain protein PERIOD (PER) and itsC. elegansorthologue LIN-42 have been proposed to constitute an evolutionary link between two distinct, circadian and developmental, timing systems. However, while the function of PER in animal circadian rhythms is well understood molecularly and mechanistically, this is not true for LIN-42’s function in timing rhythmic development. Here, using targeted deletions, we find that the LIN-42 PAS domains are dispensable for the protein’s function in timing molts. Instead, we observe arrhythmic molts upon deletion of a distinct sequence element, conserved with PER. We show that this element, designated CK1δ-binding domain (CK1BD), mediates stable binding to KIN-20, theC. elegansCK1δ/ε orthologue. We demonstrate that CK1δ phosphorylates LIN-42 and define two conserved helical motifs in the CK1BD, CK1BD-A and CK1BD-B, that have distinct roles in controlling CK1δ-binding and kinase activityin vitro. KIN-20 and the LIN-42 CK1BD are required for proper molting timingin vivo, and loss of LIN-42 binding changes KIN-20 subcellular localization. The interactions mirror the central role of a stable circadian PER–CK1 complex in setting a robust ∼24-hour period. Hence, our results establish LIN-42/PER – KIN-20/CK1δ/ε as a functionally conserved signaling module of two distinct chronobiological systems.