Protein kinase C modulates the phase-delaying effects of light in the mammalian circadian clock

Boyoung Lee, Akshata Almad, Greg Q. Butcher, Karl Obrietan

Research output: Contribution to journalArticle

Abstract

The mammalian circadian pacemaker located in the suprachiasmatic nuclei (SCN) drives a vast array of biochemical and physiological processes with 24-h periodicity. The phasing of SCN pacemaker activity is tightly regulated by photic input from the retina. Recent work has implicated protein kinase C (PKC) as a regulator of photic input, although stimulus-induced PKC activity has not been examined. Here we used a combination of biochemical, immunohistochemical and behavioral techniques to examine both the regulation and role of PKC in light-induced clock entrainment in mice. We report that photic stimulation during the subjective night, but not during the subjective day, stimulates PKC activity within the SCN. To assess the role of PKC in clock entrainment, we employed an in-vivo infusion approach to deliver the PKC inhibitor bisindolylmaleimide I to the SCN. The disruption of PKC activity significantly enhanced the phase-shifting effects of light, indicating that PKC functions as a negative regulator of light entrainment. Importantly, bisindolylmaleimide I infusion in the absence of light treatment did not phase shift the clock, demonstrating that transient disruption of basal PKC activity does not affect inherent pacemaker activity. The capacity of light to stimulate immediate early gene expression in the SCN was not substantively altered by PKC inhibition, suggesting that PKC does not couple light to rapid transcriptional activation. Rather, a combination of in-vivo and cell culture assays indicates that PKC functions as an inhibitor of PERIOD1 degradation. Thus, PKC may influence clock entrainment via a post-translational mechanism that influences clock protein stability.

Original languageEnglish (US)
Pages (from-to)451-462
Number of pages12
JournalEuropean Journal of Neuroscience
Volume26
Issue number2
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Fingerprint

Circadian Clocks
Protein Kinase C
Light
Suprachiasmatic Nucleus
Biochemical Phenomena
Physiological Phenomena
Photic Stimulation
Immediate-Early Genes
Protein C Inhibitor
Protein Stability
Periodicity
Protein Kinase Inhibitors
Transcriptional Activation
Retina

Keywords

  • Mouse
  • Period 1
  • Period 2
  • Post-translational
  • Protein kinase C
  • Suprachiasmatic nuclei

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Protein kinase C modulates the phase-delaying effects of light in the mammalian circadian clock. / Lee, Boyoung; Almad, Akshata; Butcher, Greg Q.; Obrietan, Karl.

In: European Journal of Neuroscience, Vol. 26, No. 2, 01.07.2007, p. 451-462.

Research output: Contribution to journalArticle

Lee, Boyoung ; Almad, Akshata ; Butcher, Greg Q. ; Obrietan, Karl. / Protein kinase C modulates the phase-delaying effects of light in the mammalian circadian clock. In: European Journal of Neuroscience. 2007 ; Vol. 26, No. 2. pp. 451-462.
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