Per2 phosphorylation tied to sleep disorder

A genetic mutation could help unlock the secrets of the molecular clock

Jeffrey M. Perkel
Sep 19, 2006
A human sleep disorder than disrupts circadian rhythms has provided new insights into the post-translational controls governing the molecular clock, according to a new paper in Genes and Development. Achim Kramer, professor of chronobiology at Charité Universitätsmedizin Berlin, and colleagues mapped 21 in vivo phosphorylation sites in the protein PERIOD (Per) 2, one of which corresponds to the site of a known mutation in human familial advanced sleep phase syndrome (FASPS), a disorder that advances the internal clock by four or five hours, causing people to go to sleep very early in the evening and rise very early in the morning. The FASPS mutation changes a conserved serine residue (Ser659 in the mouse) to glycine, and the authors demonstrated in a cell culture system that lack of phosphorylation at this site accelerates nuclear export and degradation of the Per2 protein. The team also demonstrated that alternate phosphorylation events...