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

Vladimira Jakubcakova; Henrik Oster; Filippo Tamanini; Cristina Cadenas; Michael Leitges; Gijsbertus T J van der Horst; Gregor Eichele

doi:10.1016/j.neuron.2007.04.031

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.

Authors

Vladimira Jakubcakova¹, Henrik Oster, Filippo Tamanini, Cristina Cadenas, Michael Leitges, Gijsbertus T J van der Horst, Gregor Eichele

Affiliation

¹ Department of Genes and Behavior, Max Planck Institute of Biophysical Chemistry, 37077 Goettingen, Germany.

PMID: 17553429
DOI: 10.1016/j.neuron.2007.04.031

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 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

Substances

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