title: PKCγ participates in food entrainment by regulating BMAL1.
abstract: Temporally restricted feeding (RF) can phase reset the circadian clocks in numerous tissues in mammals, contributing to altered timing of behavioral and physiological rhythms. However, little is known regarding the underlying molecular mechanism. Here we demonstrate a role for the gamma isotype of protein kinase C (PKCγ) in food-mediated entrainment of behavior and the molecular clock. We found that daytime RF reduced late-night activity in wild-type mice but not mice homozygous for a null mutation of PKCγ (PKCγ(-/-)). Molecular analysis revealed that PKCγ exhibited RF-induced changes in activation patterns in the cerebral cortex and that RF failed to substantially phase shift the oscillation of clock gene transcripts in the absence of PKCγ. PKCγ exerts effects on the clock, at least in part, by stabilizing the core clock component brain and muscle aryl hydrocarbon receptor nuclear translocator like 1 (BMAL1) and reducing its ubiquitylation in a deubiquitination-dependent manner. Taken together, these results suggest that PKCγ plays a role in food entrainment by regulating BMAL1 stability.
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94158, USA.
authors.forename: Luoying
authors.initials: L
authors.lastname: Zhang
authors.forename: Diya
authors.initials: D
authors.lastname: Abraham
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Lin
authors.forename: Henrik
authors.initials: H
authors.lastname: Oster
authors.forename: Gregor
authors.initials: G
authors.lastname: Eichele
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Fu
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ptáček
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004435:Eating / Q000235:genetics / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009154:Mutation; D017440:Photoperiod; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055550:Protein Stability; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; C087857:protein kinase C gamma; D011493:Protein Kinase C