Frq-ck1 interaction underlies temperature compensation of the neurospora circadian clock

Yue Hu, Xiaolan Liu, Qiaojia Lu, Yulin Yang, Qun He, Yi Liu, Xiao Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Temperature compensation is a fundamental property of all circadian clocks; temperature compensation results in a relatively constant period length at different physiological temperatures, but its mechanism is unclear. Formation of a stable complex between clock proteins and casein kinase 1 (CK1) is a conserved feature in eukaryotic circadian mechanisms. Here, we show that the FRQ-CK1 interaction and CK1-mediated FRQ phosphorylation, not FRQ stability, are main mechanisms responsible for the circadian temperature compensation phenotypes in Neurospora. Inhibition of CK1 kinase activity impaired the temperature compensation profile. Importantly, both the loss of temperature compensation and temperature overcompensation phenotypes of the wild-type and different clock mutant strains can be explained by temperature-dependent alterations of the FRQ-CK1 interaction. Furthermore, mutations that were designed to specifically affect the FRQ-CK1 interaction resulted in impaired temperature compensation of the clock. Together, these results reveal the temperature-compensated FRQ-CK1 interaction, which results in temperature-compensated CK1-mediated FRQ and WC phosphorylation, as a main biochemical process that underlies the mechanism of circadian temperature compensation in Neurospora. IMPORTANCE Temperature compensation allows clocks to adapt to all seasons by having a relatively constant period length at different physiological temperatures, but the mechanism of temperature compensation is unclear. Stability of clock proteins was previously proposed to be a major factor that regulated temperature com-pensation. In this study, we showed that the interaction between CK1 and FRQ, but not FRQ stability, explains the circadian temperature compensation phenotypes in Neurospora. This study uncovered the key biochemical mechanism responsible for temperature compensation of the circadian clock and further established the mechanism for period length determination in Neurospora. Because the regulation of circadian clock proteins by CK1 and the formation of a stable clock complex with CK1 are highly conserved in eukaryotic clocks, a similar mechanism may also exist in animal clocks.

Original languageEnglish (US)
Article numbere01425-21
JournalmBio
Volume12
Issue number3
DOIs
StatePublished - 2021

Keywords

  • Casein kinase 1
  • Circadian clock
  • Neurospora
  • Protein phosphorylation
  • Temperature compensation

ASJC Scopus subject areas

  • Microbiology
  • Virology

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