Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock

Satoru Masubuchi, Tianyan Gao, Audrey O'Neill, Kristin Eckel-Mahan, Alexandra C. Newton, Paolo Sassone-Corsi

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1) differentially attenuates Akt, PKC, and ERK1/2 signaling, thereby controlling the duration and amplitude of responses evoked by these kinases. PHLPP1 is expressed in the mammalian central clock, the suprachiasmatic nucleus, where it oscillates in a circadian fashion. To explore the role of PHLPP1 in vivo, we have generated mice with a targeted deletion of the PHLPP1 gene. Hereweshowthat PHLPP1-null mice, although displaying normal circadian rhythmicity, have a drastically impaired capacity to stabilize the circadian period after light-induced resetting, producing a large phase shift after light resetting. Our findings reveal that PHLPP1 exerts a previously unappreciated role in circadian control, governing the consolidation of circadian periodicity after resetting.

Original languageEnglish
Pages (from-to)1642-1647
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number4
DOIs
StatePublished - Jan 26 2010

Keywords

  • After-effect
  • Per
  • Period
  • Phase shift
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • General

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