Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock.
Biological rhythms are driven in mammals by a central circadian clock located in the suprachiasmatic nucleus (SCN). Light-induced phase shifting of this clock is correlated with phosphorylation of CREB at Ser133 in the SCN. Here, we characterize phosphorylation of CREB at Ser142 and describe its contribution to the entrainment of the clock. In the SCN, light and glutamate strongly induce CREB Ser142 phosphorylation. To determine the physiological relevance of phosphorylation at Ser142, we generated a mouse mutant, CREB(S142A), lacking this phosphorylation site. Light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN are significantly attenuated in CREB(S142A) mutants. Our findings provide genetic evidence that CREB Ser142 phosphorylation is involved in the entrainment of the mammalian clock and reveal a novel phosphorylation-dependent regulation of CREB activity.
Gau
Daniel
D
Division of Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Lemberger
Thomas
T
von Gall
Charlotte
C
Kretz
Oliver
O
Le Minh
Nguyet
N
Gass
Peter
P
Schmid
Wolfgang
W
Schibler
Ueli
U
Korf
Horst W
HW
Schütz
Günther
G
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology; D010766:Phosphorylation; D013493:Suprachiasmatic Nucleus / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein