cAMP-dependent signaling as a core component of the mammalian circadian pacemaker

被引：330

作者：

O'Neill, John S. ^{[1
]}

Maywood, Elizabeth S. ^{[1
]}

Chesham, Johanna E. ^{[1
]}

Takahashi, Joseph S. ^{[2
]}

Hastings, Michael H. ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England

[2] Northwestern Univ, Howard Hughes Med Inst, Dept Neurobiol & Physiol, Evanston, IL 60208 USA

来源：

SCIENCE | 2008年 / 320卷 / 5878期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1126/science.1152506

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The mammalian circadian clockwork is modeled as transcriptional and posttranslational feedback loops, whereby circadian genes are periodically suppressed by their protein products. We show that adenosine 3 ', 5 '-monophosphate (cAMP) signaling constitutes an additional, bona fide component of the oscillatory network. cAMP signaling is rhythmic and sustains the transcriptional loop of the suprachiasmatic nucleus, determining canonical pacemaker properties of amplitude, phase, and period. This role is general and is evident in peripheral mammalian tissues and cell lines, which reveals an unanticipated point of circadian regulation in mammals qualitatively different from the existing transcriptional feedback model. We propose that daily activation of cAMP signaling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles.

引用

页码：949 / 953

页数：5

共 25 条

[1] NEGATIVE FEEDBACK DEFINING A CIRCADIAN CLOCK - AUTOREGULATION OF THE CLOCK GENE-FREQUENCY [J].