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Nat Commun. 2019 Sep 25;10(1):4352. doi: 10.1038/s41467-019-12239-w.

FRQ-CK1 interaction determines the period of circadian rhythms in Neurospora.

Author information

1
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9040, USA.
2
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
3
Key Laboratory of Biopesticides and Chemical Biology, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou, Fujian, 350002, China.
4
Department of Mathematics, Universidad del Valle, Cali, 760032, Colombia.
5
State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
6
Department of Mathematical Sciences, University of Cincinnati, Cincinnati, 45221, USA.
7
Division of Statistics and Data Science, University of Cincinnati, Cincinnati, 45221, USA.
8
Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, 45267, USA.
9
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333, Burnet Avenue, Cincinnati, USA.
10
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9040, USA. Yi.Liu@UTSouthwestern.edu.

Abstract

Circadian clock mechanisms have been extensively investigated but the main rate-limiting step that determines circadian period remains unclear. Formation of a stable complex between clock proteins and CK1 is a conserved feature in eukaryotic circadian mechanisms. Here we show that the FRQ-CK1 interaction, but not FRQ stability, correlates with circadian period in Neurospora circadian clock mutants. Mutations that specifically affect the FRQ-CK1 interaction lead to severe alterations in circadian period. The FRQ-CK1 interaction has two roles in the circadian negative feedback loop. First, it determines the FRQ phosphorylation profile, which regulates FRQ stability and also feeds back to either promote or reduce the interaction itself. Second, it determines the efficiency of circadian negative feedback process by mediating FRQ-dependent WC phosphorylation. Our conclusions are further supported by mathematical modeling and in silico experiments. Together, these results suggest that the FRQ-CK1 interaction is a major rate-limiting step in circadian period determination.

PMID:
31554810
PMCID:
PMC6761100
DOI:
10.1038/s41467-019-12239-w
[Indexed for MEDLINE]
Free PMC Article

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