Your browser doesn't support javascript.
loading
Cryptochrome proteins regulate the circadian intracellular behavior and localization of PER2 in mouse suprachiasmatic nucleus neurons.
Smyllie, Nicola J; Bagnall, James; Koch, Alex A; Niranjan, Dhevahi; Polidarova, Lenka; Chesham, Johanna E; Chin, Jason W; Partch, Carrie L; Loudon, Andrew S I; Hastings, Michael H.
Affiliation
  • Smyllie NJ; Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
  • Bagnall J; Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.
  • Koch AA; Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.
  • Niranjan D; Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
  • Polidarova L; Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
  • Chesham JE; Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
  • Chin JW; Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0H, United Kingdom.
  • Partch CL; Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 96064.
  • Loudon ASI; Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.
  • Hastings MH; Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; mha@mrc-lmb.cam.ac.uk.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in En | MEDLINE | ID: mdl-35046033
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 PER2Venus 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.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Circadian Rhythm / Cryptochromes / Period Circadian Proteins / Suprachiasmatic Nucleus Neurons Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Document type: Article Affiliation country: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Circadian Rhythm / Cryptochromes / Period Circadian Proteins / Suprachiasmatic Nucleus Neurons Limits: Animals Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Document type: Article Affiliation country: Reino Unido