REGULATION OF CREB PHOSPHORYLATION IN THE SUPRACHIASMATIC NUCLEUS BY LIGHT AND A CIRCADIAN CLOCK
REGULATION OF CREB PHOSPHORYLATION IN THE SUPRACHIASMATIC NUCLEUS BY LIGHT AND A CIRCADIAN CLOCK
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DOI：
10.1126/science.8097062
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发表时间：
1993-04-09
期刊：
影响因子：
56.9
通讯作者：
GREENBERG, ME
中科院分区：
文献类型：
--
作者：
GINTY, DD;KORNHAUSER, JM;GREENBERG, ME
哺乳动物的昼夜节律是由下丘脑视交叉上核（SCN）内的起搏器调节的。控制昼夜节律起搏器同步的分子机制尚不清楚；然而，即时早期基因（IEG）在SCN中的表达与SCN调节的节律的夹带密切相关。分离出识别转录因子环腺苷单磷酸反应元件结合蛋白（CREB）活化磷酸化形式的抗体。仓鼠暴露于光后几分钟内，SCN中的CREB在转录调控位点Ser133上发生磷酸化。CREB磷酸化依赖于昼夜节律时间：在昼夜节律周期中，当光诱导IEG表达并引起昼夜节律的相移时，CREB才会被磷酸化。这些结果暗示CREB参与下丘脑的神经元信号传导，并表明SCN中光调节分子反应的生物钟门控发生在CREB磷酸化的上游。
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.