Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock.
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.
Masubuchi
Satoru
S
Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA.
Gao
Tianyan
T
O'Neill
Audrey
A
Eckel-Mahan
Kristin
K
Newton
Alexandra C
AC
Sassone-Corsi
Paolo
P
D000818:Animals; D002940:Circadian Rhythm / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D009687:Nuclear Proteins; D016875:tau Proteins; C519282:PHLPP1 protein, mouse; D010749:Phosphoprotein Phosphatases