ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Distinct and separable roles for endogenous CRY1 and CRY2 within the circadian molecular clockwork of the suprachiasmatic nucleus, as revealed by the Fbxl3(Afh) mutation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.The American journal of clinical nutrition · 2014Trial
- PERfect Day: reversible and dose-dependent control of circadian time-keeping in the mouse suprachiasmatic nucleus by translational switching of PERIOD2 protein expression.The European journal of neuroscience · 2024Article
- The Function, Regulation, and Mechanism of Protein Turnover in Circadian Systems inInternational journal of molecular sciences · 2024Review
- Association between PER and CRY gene polymorphisms and the response to caffeine citrate treatment in infants with apnea of prematurity.Frontiers in pediatrics · 2024Article
- A conditionalScience advances · 2023Article
- Cryptochromes in mammals: a magnetoreception misconception?Frontiers in physiology · 2023Review
- Article
- Cryptochrome 1 as a state variable of the circadian clockwork of the suprachiasmatic nucleus: Evidence from translational switching.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.Bipolar disorders · 2022Review
- Single-cell transcriptomics of suprachiasmatic nuclei reveal a Prokineticin-driven circadian network.The EMBO journal · 2021Article
- CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping.The EMBO journal · 2021Article
- The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair.Nature communications · 2021Article
- CRY1-CBS binding regulates circadian clock function and metabolism.The FEBS journal · 2021Article
- Suppression of circadian clock protein cryptochrome 2 promotes osteoarthritis.Osteoarthritis and cartilage · 2020Article
- Orchestration of Circadian Timing by Macromolecular Protein Assemblies.Journal of molecular biology · 2020Review
- Article
- Neural circuit repair by low-intensity magnetic stimulation requires cellular magnetoreceptors and specific stimulation patterns.Science advances · 2019Article
- Translational switching of Cry1 protein expression confers reversible control of circadian behavior in arrhythmic Cry-deficient mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- JMJD5 links CRY1 function and proteasomal degradation.PLoS biology · 2018Article
- Differential roles for cryptochromes in the mammalian retinal clock.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
The circadian clock of the suprachiasmatic nucleus (SCN) drives daily rhythms of behavior. Cryptochromes (CRYs) are powerful transcriptional repressors within the molecular negative feedback loops at the heart of the SCN clockwork, where they periodically suppress their own expression and that of clock-controlled genes. To determine the differential contributions of CRY1 and CRY2 within circadian timing in vivo, we exploited the N-ethyl-N-nitrosourea-induced afterhours mutant Fbxl3(Afh) to stabilize endogenous CRY. Importantly, this was conducted in CRY2- and CRY1-deficient mice to test each CRY in isolation. In both CRY-deficient backgrounds, circadian rhythms of wheel-running and SCN bioluminescence showed increased period length with increased Fbxl3(Afh) dosage. Although both CRY proteins slowed the clock, CRY1 was significantly more potent than CRY2, and in SCN slices, CRY1 but not CRY2 prolonged the interval of transcriptional suppression. Selective CRY-stabilization demonstrated that both CRYs are endogenous transcriptional repressors of clock-controlled genes, but again CRY1 was preeminent. Finally, although Cry1(-/-);Cry2(-/-) mice were behaviorally arrhythmic, their SCN expressed short period (~18 h) rhythms with variable stability. Fbxl3(Afh/Afh) had no effect on these CRY-independent rhythms, confirming its circadian action is mediated exclusively via CRYs. Thus, stabilization of both CRY1 and CRY2 are necessary and sufficient to explain circadian period lengthening by Fbxl3(Afh/Afh). Both CRY proteins dose-dependently lengthen the intrinsic, high-frequency SCN rhythm, and CRY2 also attenuates the more potent period-lengthening effects of CRY1. Incorporation of CRY-mediated transcriptional feedback thus confers stability to intrinsic SCN oscillations, establishing periods between 18 and 29 h, as determined by selective contributions of CRY1 and CRY2.
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