Abstract
Light is the most potent stimulus for synchronizing endogenous circadian rhythms with external time. Photic clock resetting in mammals involves cAMP-responsive element binding protein (CREB)-mediated transcriptional activation of Period clock genes in the suprachiasmatic nuclei (SCN). Here we provide evidence for an additional photic input pathway to the mammalian circadian clock based on Protein Kinase C α (PRKCA). We found that Prkca-deficient mice show an impairment of light-mediated clock resetting. In the SCN of wild-type mice, light exposure evokes a transient interaction between PRKCA and PERIOD 2 (PER2) proteins that affects PER2 stability and nucleocytoplasmic distribution. These posttranslational events, together with CREB-mediated transcriptional regulation, are key factors in the molecular mechanism of photic clock resetting.
| Original language | English |
|---|---|
| Journal | Neuron |
| Volume | 54 |
| Issue number | 5 |
| Pages (from-to) | 831-843 |
| Number of pages | 13 |
| ISSN | 0896-6273 |
| DOIs | |
| Publication status | Published - 07.06.2007 |
Funding
We thank Drs. Parker and Mischak for providing the kdPRKCA construct and recombinant PRKCA. Thanks to Dr. Kazuhiro Yagita (University of Nagoya) for the PER2 EGFP expression plasmid, Erik Engelen (EUMC Rotterdam) for technical assistance, and Dr. Pablo Szendro for useful discussions. This work was supported by EU grant QLG3-CT-2002-01829. G.T.J.v.d.H. received support from SenterNovem (project BSIK030503). H.O. was supported in part by an Otto Hahn Medal fellowship from the Max Planck Society.
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
