Editors' ChoiceCircadian Rhythms

Hey, That Clock Is Fast

See allHide authors and affiliations

Science's STKE  05 Apr 2005:
Vol. 2005, Issue 278, pp. tw122
DOI: 10.1126/stke.2782005tw122

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 CKIδ 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 CKIδ 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. Ptáček, Y.-H. Fu, Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome. Nature 434, 640-644 (2005). [PubMed]