The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1
Document Type
Journal ArticlePublication Date
2011-09-27Keywords
AnimalsCasein Kinase I
*Circadian Rhythm
Electrophoresis, Polyacrylamide Gel
Mice
Period Circadian Proteins
Phosphorylation
Protein Phosphatase 1
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Mounting evidence suggests that PERIOD (PER) proteins play a central role in setting the speed (period) and phase of the circadian clock. Pharmacological and genetic studies have shown that changes in PER phosphorylation kinetics are associated with changes in circadian rhythm period and phase, which can lead to sleep disorders such as Familial Advanced Sleep Phase Syndrome in humans. We and others have shown that casein kinase 1delta and epsilon (CK1delta/epsilon) are essential PER kinases, but it is clear that additional, unknown mechanisms are also crucial for regulating the kinetics of PER phosphorylation. Here we report that circadian periodicity is determined primarily through PER phosphorylation kinetics set by the balance between CK1delta/epsilon and protein phosphatase 1 (PP1). In CK1delta/epsilon-deficient cells, PER phosphorylation is severely compromised and nonrhythmic, and the PER proteins are constitutively cytoplasmic. However, when PP1 is disrupted, PER phosphorylation is dramatically accelerated; the same effect is not seen when PP2A is disrupted. Our work demonstrates that the speed and rhythmicity of PER phosphorylation are controlled by the balance between CK1delta/epsilon and PP1, which in turn determines the period of the circadian oscillator. Thus, our findings provide clear insights into the molecular basis of how the period and phase of our daily rhythms are determined.Source
Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16451-6. Epub 2011 Sep 19. Link to article on publisher's siteDOI
10.1073/pnas.1107178108Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37848PubMed ID
21930935Related Resources
Link to Article in PubMedRights
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/misc/authorfaq.shtml.ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1107178108