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A conserved chronobiological complex times C. elegans development.

Rebecca K SpanglerGuinevere E AshleyKathrin BraunDaniel WruckAndrea Ramos-CoronadoJames Matthew RagleVytautas IesmantaviciusDaniel HessCarrie L PartchHelge GroßhansJordan D Ward
Published in: bioRxiv : the preprint server for biology (2024)
The mammalian PAS-domain protein PERIOD (PER) and its C. elegans orthologue 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 the function of LIN-42 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 mediates stable binding to KIN-20, the C. elegans CK1δ/ε orthologue. We demonstrate that CK1δ phosphorylates LIN-42 and define two conserved helical motifs, CK1δ-binding domain A (CK1BD-A) and CK1BD-B, that have distinct roles in controlling CK1δ-binding and kinase activity in vitro . KIN-20 and the LIN-42 CK1BD are required for proper molting timing in vivo . These 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.
Keyphrases
  • protein kinase
  • transcription factor
  • blood pressure
  • gene expression
  • dna binding
  • drug delivery