Light entrainment of the mammalian circadian clock by a PRKCA-dependent posttranslational mechanism.
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.
Jakubcakova
Vladimira
V
Department of Genes and Behavior, Max Planck Institute of Biophysical Chemistry, 37077 Goettingen, Germany.
Oster
Henrik
H
Tamanini
Filippo
F
Cadenas
Cristina
C
Leitges
Michael
M
van der Horst
Gijsbertus T J
GT
Eichele
Gregor
G
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000235:genetics* / Q000528:radiation effects; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D002940:Circadian Rhythm / Q000235:genetics* / Q000528:radiation effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010775:Photic Stimulation; D017440:Photoperiod; D051571:Protein Kinase C-alpha / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000502:physiology* / Q000528:radiation effects; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000528:radiation effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors; C496630:Prkca protein, mouse; D051571:Protein Kinase C-alpha