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<p>The mammalian protein PERIOD (PER) and its<i> C. elegans</i> orthologue LIN-42 have been proposed to constitute an evolutionary link between two distinct, circadian and developmental, timing systems. 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, reflected in <i>C. elegans</i> molting cycles. We observed arrhythmic molts upon combined deletion of a region comprising two distinct sequence elements previously termed SYQ and LT. This region functions as a casein kinase I (CK1)-binding domain (CK1BD) mediating stable binding to KIN-20, the <i>C. elegans</i> CK1δ/ε orthologue. CK1 phosphorylates LIN-42, and the CK1BD sub-domains SYQ/CKBD-A and LT/CKBD-B play distinct roles in controlling CK1-binding and kinase activity in vitro. KIN-20 and the LIN-42 CK1BD are required for proper molt timing in vivo, and loss of LIN-42 binding or of the phosphorylated LIN-42 tail impairs nuclear accumulation of KIN-20. These findings indicate that LIN-42/PER and KIN-20/CK1 form a functionally conserved signaling module of two distinct chronobiological systems.</p>

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A conserved chronobiological complex times C. elegans development

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月20日

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  • Rebecca K Spangler,
  • Kathrin Braun,
  • Guinevere E Ashley,
  • Marit van der Does,
  • Daniel Wruck,
  • Andrea Ramos Coronado,
  • James Matthew Ragle,
  • Vytautas Iesmantavicius,
  • Lucas J Morales Moya,
  • Keya Daly,
  • Carrie L Partch,
  • Helge Großhans,
  • Jordan D Ward

摘要

The mammalian 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. 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, reflected in C. elegans molting cycles. We observed arrhythmic molts upon combined deletion of a region comprising two distinct sequence elements previously termed SYQ and LT. This region functions as a casein kinase I (CK1)-binding domain (CK1BD) mediating stable binding to KIN-20, the C. elegans CK1δ/ε orthologue. CK1 phosphorylates LIN-42, and the CK1BD sub-domains SYQ/CKBD-A and LT/CKBD-B play distinct roles in controlling CK1-binding and kinase activity in vitro. KIN-20 and the LIN-42 CK1BD are required for proper molt timing in vivo, and loss of LIN-42 binding or of the phosphorylated LIN-42 tail impairs nuclear accumulation of KIN-20. These findings indicate that LIN-42/PER and KIN-20/CK1 form a functionally conserved signaling module of two distinct chronobiological systems.