CHRONO and DEC1/DEC2 compensate for lack of CRY1/CRY2 in expression of coherent circadian rhythm but not in generation of circadian oscillation in the neonatal mouse SCN

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Sept. 28, 2021

Abstract Clock genes Cry1 and Cry2 , inhibitory components of core molecular feedback loop, are regarded as critical molecules for the circadian rhythm generation in mammals. A double knockout abolishes behavioral adult mice under constant darkness. However, robust rhythms PER2::LUC expression detected cultured suprachiasmatic nucleus (SCN) / deficient neonatal restored SCN by co-culture with wild-type SCN. These findings led us to postulate compensatory molecule(s) Cry1/Cry2 deficiency generation. We examined roles Chrono Dec1/Dec2 proteins, suppressors Per(s) transcription similar CRY(s). Unexpectedly, or Dec1 Dec2 did not abolish but decoupled coherent into three different periodicities significantly shortened period DNA microarray analysis revealed substantial increases Per (s), Dec (s) expression, indicating disinhibition transactivation BMAL1/CLOCK. Here, we conclude that do compensate absence CRY1/CRY2 contribute mouse most likely through integration cellular rhythms.

Language: Английский

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Rhythms in lipid droplet content driven by a metabolic oscillator are conserved throughout evolution

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Aug. 13, 2024

The biological clock in eukaryotes controls daily rhythms physiology and behavior. It displays a complex organization that involves the molecular transcriptional redox oscillator which may coordinately work to control cellular rhythms. has emerged very early evolution adaptation environmental changes O

Language: Английский

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Evolution of casein kinase 1 and functional analysis of new doubletime mutants in Drosophila

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 14, 2022

Circadian clocks are timing devices that rhythmically adjust organism’s behavior, physiology, and metabolism to the 24-h day-night cycle. Eukaryotic circadian rely on several interlocked transcription-translation feedback loops, where protein stability is key part of delay between transcription appearance mature proteins within loops. In bilaterian animals, including mammals insects, clock depends a homologous set proteins. Despite mostly conserved components among fruit fly Drosophila mammals, lineage-specific differences exist. Here we have systematically explored evolution sequence variability insect DBT their vertebrate homologs casein kinase 1 delta (CKIδ) epsilon (CKIε), dated origin separation CKIδ from CKIε, identified at least three additional independent duplications CKIδ/ε gene in Petromyzon , Danio Xenopus . We determined regions specific Diptera, functionally tested subset those D. melanogaster Replacement Lysine K224 with acidic residues strongly impacts free-running period even heterozygous flies, whereas homozygous mutants not viable. K224D temperature compensation defect longer periods higher temperatures, which exactly opposite trend what was reported for corresponding mammalian mutants. All DBTs dipteran insects contain NKRQK motif positions 220–224. The occurrence this perfectly correlates presence BRIDE OF DOUBLETIME, BDBT, Diptera. BDBT non-canonical FK506-binding physically interacts DBT. phylogeny suggests either absent or highly modified non-dipteran insects. addition silico analysis DBT/CKIδ/ε diversity, four novel genes genus

Language: Английский

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CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: May 16, 2020

Abstract The daily organisation of most mammalian cellular functions is attributed to circadian regulation clock-controlled protein expression, driven by cycles CRYPTOCHROME-dependent transcriptional feedback repression. To test this, we compared the proteome and phosphoproteome wild type CRY-deficient fibroblast cells. Strikingly, cells showed a two-fold increase in circadian-regulated proteins, phosphopeptides, K + transport. This was accompanied extensive remodelling overall, including reduced phosphatase proteasome subunit expression. These adaptations rendered more sensitive stress, which may account for their robustness contribute wide-ranging phenotypes mice. We suggest that CRY ultimately suppress, rather than generate, rhythms abundance, thereby maintaining osmotic homeostasis.

Language: Английский

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Circadian gene × environment perturbations influence alcohol drinking in Cryptochrome ‐deficient mice

Addiction Biology, Journal Year: 2021, Volume and Issue: 27(1)

Published: Oct. 20, 2021

Alcohol use disorder (AUD) is a widespread addiction with severe consequences for health. AUD patients often suffer from sleep disturbances and irregular daily patterns. Conversely, disruptions of circadian rhythms are considered risk factor alcohol relapses. In this study, we investigated the extent to which genetic environmental their interaction alter drinking behaviour in mice. As model disruption, used Cryptochrome1/2-deficient (Cry1/2-/- ) mice strongly suppressed found that they exhibit significantly reduced preference but increased incentive motivation obtain it. Similarly, low SCN amplitude correlates WT Moreover, show Cry1/2-/- concurs high corticosterone levels orexin precursor prepro-orexin respond differently withdrawal. environmentally induced disruption rhythms, exposed "shift work" light/dark regimen, also leads reduction preference. Interestingly, effect even more pronounced when perturbations interact under conditions. conclusion, our study demonstrates mice, have effects on consumption as well physiological factors other behaviours associated between further alters behaviour.

Language: Английский

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