The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization
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Le résumé fourni par la source
Circadian clocks are molecular timekeeping mechanisms that allow organisms to anticipate daily changes in their environment. The fundamental cellular basis of these clocks is delayed negative feedback gene regulation with PERIOD and CRYPTOCHROME containing protein complexes as main inhibitory elements. For a correct circadian period, it is essential that such clock protein complexes accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly understood. We performed a systematic RNAi-mediated screen in human cells and identified 15 genes associated with the nucleo-cytoplasmic translocation machinery, whose expression is important for circadian clock dynamics. Among them was Transportin 1 (TNPO1), a non-classical nuclear import carrier, whose knockdown and knockout led to short circadian periods. TNPO1 was found in endogenous clock protein complexes and particularly binds to PER1 regulating its (but not PER2's) nuclear localization. While PER1 is also transported to the nucleus by the classical, Importin β-mediated pathway, TNPO1 depletion slowed down PER1 nuclear import rate as revealed by fluorescence recovery after photobleaching (FRAP) experiments. In addition, we found that TNPO1-mediated nuclear import may constitute a novel input pathway of how cellular redox state signals to the clock, since redox stress increases binding of TNPO1 to PER1 and decreases its nuclear localization. Together, our RNAi screen knocking down import carriers (but also export carriers) results in short and long circadian periods indicating that the regulatory pathways that control the timing of clock protein subcellular localization are far more complex than previously assumed. TNPO1 is one of the novel players essential for normal circadian periods and potentially for redox regulation of the clock.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization
- Date Crossref
- 29/01/2018
- Éditeur
- Public Library of Science (PLoS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Charité - Universitätsmedizin Berlin pays non établi dans la noticeÉtablissement de santé
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LMU Klinikum pays non établi dans la noticeÉtablissement de santé
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Max Planck Institute of Biochemistry Department of Proteomics and Signal Transduction pays non établi dans la noticeStructure de recherche
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Ludwig-Maximilians-Universität München pays non établi dans la noticeUniversité ou école supérieure
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Humboldt-Universität zu Berlin pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Chronobiology pays non établi dans la noticeStructure de recherche
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Institute of Medical Psychology pays non établi dans la noticeStructure de recherche
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Molecular Biophysics pays non établi dans la noticeInstitution
Charité - Universitätsmedizin Berlin, LMU Klinikum et Department of Proteomics and Signal Transduction — Max Planck Institute of Biochemistry, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.