Light entrainment of the mammalian circadian clock by a PRKCA-dependent posttranslational mechanism

Neuron. 2007 Jun 7;54(5):831-43. doi: 10.1016/j.neuron.2007.04.031.


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 alpha (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Biological Clocks / genetics*
  • Biological Clocks / radiation effects
  • COS Cells
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chlorocebus aethiops
  • Circadian Rhythm / genetics*
  • Circadian Rhythm / radiation effects
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Down-Regulation / genetics
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • Photic Stimulation
  • Photoperiod*
  • Protein Kinase C-alpha / genetics*
  • Protein Processing, Post-Translational / physiology*
  • Protein Processing, Post-Translational / radiation effects
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Suprachiasmatic Nucleus / metabolism*
  • Suprachiasmatic Nucleus / radiation effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Cell Cycle Proteins
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Nuclear Proteins
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Transcription Factors
  • Prkca protein, mouse
  • Protein Kinase C-alpha