CIRCADIAN RHYTHMS Hey, That Clock Is Fast

If you like to "burn the midnight oil," you'll find it hard to imagine the behavior of humans who have a defect in signaling by CKI (casein kinase I), a protein kinase that participates in the biochemical machinery that establishes circadian rhythms. Affected individuals go to sleep early and awaken early in the morning. To explore the molecular mechanisms behind this sleep syndrome, known as FASPS (familial advanced sleep phase syndrome), Xu et al. characterized a mutation in the CKI gene from a family afflicted with FASPS. The encoded kinase had decreased catalytic activity in vitro. Transgenic mice engineered to express the mutation had a circadian period that was shorter than normal, as do the human patients noted above. Thus, the authors conclude that CKI is an important component of the mammalian clock. The components of the clock are generally evolutionarily conserved between mammals and fruit flies and are controlled by similar phosphorylation mechanisms, but when transgenic flies were created that expressed the mutant CKI, they actually had a lengthened circadian period. Thus, although the "parts list" is similar, clock assembly in flies and mammals appears to differ. Nevertheless, both mechanisms provide the animals with similar timing functions.

Y. Xu, Q. S. Padiath, R. E. Shapiro, C. R. Jones, S. C. Wu, N. Saigoh, K. Saigoh, L. J. Ptáek, Y.-H. Fu, Functional consequences of a CKI mutation causing familial advanced sleep phase syndrome. Nature 434, 640-644 (2005). [PubMed]

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DATABASE OF CELL SIGNALING
Drosophila Circadian Pathway

Russell N. Van Gelder
Sci. Signal. (Connections Map Pathway), http://stke.sciencemag.org/cgi/cm/stkecm;CMP_13296
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