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

Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1642-7. doi: 10.1073/pnas.0910292107. Epub 2010 Jan 4.

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. Here we show that 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / radiation effects*
  • Gene Expression Regulation / radiation effects
  • Light*
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / metabolism*
  • Phosphoprotein Phosphatases / deficiency
  • Phosphoprotein Phosphatases / metabolism*
  • tau Proteins / metabolism

Substances

  • Nuclear Proteins
  • tau Proteins
  • PHLPP1 protein, mouse
  • Phosphoprotein Phosphatases