ArticleProceedings of the National Academy of Sciences of the United States of America2022
Cryptochrome proteins regulate the circadian intracellular behavior and localization of PER2 in mouse suprachiasmatic nucleus neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- Roux-en-Y gastric bypass alters microbial circadian rhythms with links to metabolic improvement.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.eLife · 2026Article
- Core clock protein subcellular dynamics coordinate local and global circadian control in syncytia.The Journal of cell biology · 2026Article
- Decoding darkness by seeking photoreceptor functions with and without light.Nature plants · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Promoter Frame Position Affects Strength and Nature of Circadian Oscillations inInternational journal of molecular sciences · 2025Article
- Core Clock Protein Subcellular Dynamics Coordinate Local and Global Circadian Control in Syncytia.bioRxiv : the preprint server for biology · 2025Article
- Decrypting the Nonadiabatic Photoinduced Electron Transfer Mechanism in Light-Sensing Cryptochrome.ACS central science · 2025Article
- Quantitative measures of clock protein dynamics in the mouse suprachiasmatic nucleus extends the circadian time-keeping model.The EMBO journal · 2025Article
- Development of compounds for targeted degradation of mammalian cryptochrome proteins.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- 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
- Cellular iron depletion enhances behavioral rhythm by limiting brain Per1 expression in mice.CNS neuroscience & therapeutics · 2024Article
- Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.bioRxiv : the preprint server for biology · 2023Article
- Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD.The Journal of cell biology · 2023Article
- Astrocytic control of extracellular GABA drives circadian timekeeping in the suprachiasmatic nucleus.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Different Approaches to Study Molecular Blueprint and Biological Behavior of Brain Tumors: Editorial to the Special Issue "Advances in Molecular Genetics of Brain Tumors".International journal of molecular sciences · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The ∼20,000 cells of the suprachiasmatic nucleus (SCN), the master circadian clock of the mammalian brain, coordinate subordinate cellular clocks across the organism, driving adaptive daily rhythms of physiology and behavior. The canonical model for SCN timekeeping pivots around transcriptional/translational feedback loops (TTFL) whereby PERIOD (PER) and CRYPTOCHROME (CRY) clock proteins associate and translocate to the nucleus to inhibit their own expression. The fundamental individual and interactive behaviors of PER and CRY in the SCN cellular environment and the mechanisms that regulate them are poorly understood. We therefore used confocal imaging to explore the behavior of endogenous PER2 in the SCN of PER2::Venus reporter mice, transduced with viral vectors expressing various forms of CRY1 and CRY2. In contrast to nuclear localization in wild-type SCN, in the absence of CRY proteins, PER2 was predominantly cytoplasmic and more mobile, as measured by fluorescence recovery after photobleaching. Virally expressed CRY1 or CRY2 relocalized PER2 to the nucleus, initiated SCN circadian rhythms, and determined their period. We used translational switching to control CRY1 cellular abundance and found that low levels of CRY1 resulted in minimal relocalization of PER2, but yet, remarkably, were sufficient to initiate and maintain circadian rhythmicity. Importantly, the C-terminal tail was necessary for CRY1 to localize PER2 to the nucleus and to initiate SCN rhythms. In CRY1-null SCN, CRY1Δtail opposed PER2 nuclear localization and correspondingly shortened SCN period. Through manipulation of CRY proteins, we have obtained insights into the spatiotemporal behaviors of PER and CRY sitting at the heart of the TTFL molecular mechanism.
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