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Abstract
Circadian rhythms are endogenous oscillations in nearly all organisms, from prokaryotes to humans, allowing them to adapt to cyclical environments for close to 24 h. Circadian rhythms are regulated by a central clock, based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1ε/δ (CK1ε/δ) phosphorylation. In the nematode Caenorhabditis elegans, period and casein kinase 1ε/δ are conserved as lin-42 and kin-20, respectively. Here, we studied the involvement of lin-42 and kin-20 in the circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations of lin-42 and kin-20 generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and epidermal seam cells, as well as in other cells. Depletion of LIN-42 and KIN-20, specifically in neuronal cells after development, was sufficient to lengthen the period of oscillating sur-5 expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells.
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1 Universidad Nacional de Quilmes, Laboratorio de Cronobiología, Buenos Aires, Argentina (GRID:grid.11560.33) (ISNI:0000 0001 1087 5626)
2 University of California Santa Cruz, Department of Chemistry and Biochemistry, Santa Cruz, USA (GRID:grid.205975.c) (ISNI:0000 0001 0740 6917)
3 Université du Québec à Montréal, CERMO-FC Research Center, Department of Biological Sciences, Montréal, Canada (GRID:grid.38678.32) (ISNI:0000 0001 2181 0211)
4 University of California Santa Cruz, Department of Molecular, Cell & Developmental Biology, Santa Cruz, USA (GRID:grid.205975.c) (ISNI:0000 0001 0740 6917)
5 Universidad de San Andrés/CONICET, Laboratorio Interdisciplinario del Tiempo (LITERA), Buenos Aires, Argentina (GRID:grid.441741.3) (ISNI:0000 0001 2325 2241)
6 University of California Santa Cruz, Department of Chemistry and Biochemistry, Santa Cruz, USA (GRID:grid.205975.c) (ISNI:0000 0001 0740 6917); UC San Diego, Center for Circadian Biology, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
7 Université du Québec à Montréal, CERMO-FC Research Center, Department of Biological Sciences, Montréal, Canada (GRID:grid.38678.32) (ISNI:0000 0001 2181 0211); University of Massachusetts Chan Medical School, Department of Neurobiology, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364)
8 University Medical Center Groningen, European Institute for the Biology of Aging, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598)
9 Universidad Nacional de Quilmes, Laboratorio de Cronobiología, Buenos Aires, Argentina (GRID:grid.11560.33) (ISNI:0000 0001 1087 5626); Universidad de San Andrés/CONICET, Laboratorio Interdisciplinario del Tiempo (LITERA), Buenos Aires, Argentina (GRID:grid.441741.3) (ISNI:0000 0001 2325 2241)