Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-52882

Schmutz, I; Wendt, S; Schnell, A; Kramer, A; Mansuy, I M; Albrecht, U (2011). Protein phosphatase 1 (PP1) is a post-translational regulator of the mammalian circadian clock. PLoS ONE, 6(6):e21325.

[img]
Preview
Published Version
PDF
871Kb

Abstract

Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1) as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:06 Jan 2012 15:13
Last Modified:18 Dec 2013 16:36
Publisher:Public Library of Science
ISSN:1932-6203
Publisher DOI:10.1371/journal.pone.0021325
PubMed ID:21712997
Citations:Web of Science®. Times Cited: 6
Google Scholar™

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page