Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock.
Mammalian circadian rhythms are regulated by a pacemaker within the suprachiasmatic nuclei (SCN) of the hypothalamus. The molecular mechanisms controlling the synchronization of the circadian pacemaker are unknown; however, immediate early gene (IEG) expression in the SCN is tightly correlated with entrainment of SCN-regulated rhythms. Antibodies were isolated that recognize the activated, phosphorylated form of the transcription factor cyclic adenosine monophosphate response element binding protein (CREB). Within minutes after exposure of hamsters to light, CREB in the SCN became phosphorylated on the transcriptional regulatory site, Ser133. CREB phosphorylation was dependent on circadian time: CREB became phosphorylated only at times during the circadian cycle when light induced IEG expression and caused phase shifts of circadian rhythms. These results implicate CREB in neuronal signaling in the hypothalamus and suggest that circadian clock gating of light-regulated molecular responses in the SCN occurs upstream of phosphorylation of CREB.
Ginty
D D
DD
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Kornhauser
J M
JM
Thompson
M A
MA
Bading
H
H
Mayo
K E
KE
Takahashi
J S
JS
Greenberg
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002940:Circadian Rhythm; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology / Q000378:metabolism*; D003624:Darkness; D005786:Gene Expression Regulation; D016762:Genes, fos; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008027:Light; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D005971:Glutamates; D005576:Colforsin; D018698:Glutamic Acid; D011189:Potassium Chloride