First Author | Zhang L | Year | 2012 |
Journal | Proc Natl Acad Sci U S A | Volume | 109 |
Issue | 50 | Pages | 20679-84 |
PubMed ID | 23185022 | Mgi Jnum | J:193126 |
Mgi Id | MGI:5467682 | Doi | 10.1073/pnas.1218699110 |
Citation | Zhang L, et al. (2012) PKCgamma participates in food entrainment by regulating BMAL1. Proc Natl Acad Sci U S A 109(50):20679-84 |
abstractText | 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 (PKCgamma) 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 PKCgamma (PKCgamma(-/-)). Molecular analysis revealed that PKCgamma 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 PKCgamma. PKCgamma 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 PKCgamma plays a role in food entrainment by regulating BMAL1 stability. |